The dying master of the powerful Poison Clan dispatches his last pupil, Yang Tieh, on a crucial mission. Worried that the skills he has taught are being used to evil ends, he orders Yang to trace a retired colleague, Yun, and warn him that the fortune he amassed from the clan's activities is under threat from five of his former pupils, each an expert in his own lethal combat style. Yang must discover the whereabouts and true identities of these masked warriors, and decide which, if any, he can trust to join him in his mission. The five pupils are the Centipede, Snake, Scorpion, Lizard, and Toad. Centipede, Snake, Lizard and Toad know each other, but none know the Scorpion, who always wears a mask. Before he dies, the master teaches Yang the weaknesses of each style.
The Centipede and the Snake come to the Yun family house to steal money. They murder the entire family when Yun refuses to divulge the location of his fortune. A witness sees the Centipede at the house. Later, the Scorpion investigates the scene and retrieves a hidden map. The Lizard, working as a policeman, recruits the Toad to help arrest the Centipede. After the Centipede is arrested and charged with murder, the Scorpion tells the Snake to frame the Toad for the murders. The corrupt judge sends the Lizard away on government business. The Snake pays an officer to make the witness commit perjury. The Toad is framed by the witness, who tells the judge that he saw the Toad at the scene of the crime. Toad refuses to confess, and his kung fu initially makes him invulnerable to their torture. The Snake devises a torture device to counteract it. When this fails, the Scorpion secretly cripples the Toad with darts to his weak spot. Subjected to further torture, the Toad passes out, and his signature is forged on a confession.
The Centipede is acquitted of the murder charges and goes free. The officer suffocates the Toad and hangs him in the cell as if he committed suicide. The Centipede and Snake kill the witness and the corrupt officer. Two Chinese policemen in the restaurant tell the Lizard what happened to the Toad, the witness, and the officer while he was gone. The Lizard's supervisor, Chief Constable Ma, encourages him to forget the issue, but the Lizard refuses. Yang identifies the Lizard, teams with him, and together they practice techniques to defeat the others. As Yang and the Lizard prepare to confront the Centipede and the Snake, the chief constable joins them. During the fight, he reveals himself as the Scorpion and reveals that he intends to kill everyone and keep the Yun fortune for himself. The Scorpion fatally injures the Snake and bribes the Centipede into helping him. Yang and the Lizard defeat the Centipede, and the Snake helps kill the Scorpion before he, too, dies. Yang and the Lizard retrieve the Scorpion's map from his corpse, vowing to use the fortune for good to restore the reputation of the Poison Clan.Chiang Sheng as Yang Tieh, last student of the Venom House. His style is a mix and is incomplete; he must ally with one of the others to defeat the rest.
Sun Chien as Gao Ji, the Scorpion/Chief Constable Ma. His style uses deadly kicks.
Kuo Chui as Meng Tianxia, the Lizard/Constable He Yu. His style focuses on speed and gravity, and it allows him to walk on walls.
Lo Mang as Liang Shen, the Toad/Li Hao. His style gives him invulnerability. If his weak spot is attacked, his invulnerability is canceled.
Wei Pei as Qi Dong, the Snake/Hong Wentong. His style focuses on accurate strikes to vulnerable spots. His weakness is being attacked from two sides at once, which he can not defend against effectively.
Lu Feng as Zhang Yiaotian, the Centipede/Tan Shan-kui. His style focuses on speed, and his weakness is being attacked both high and low at once.
Wang Lung-wei as Justice Wang
Ku Feng as Bookkeeper Yuan
Dick Wei as dying Head of Five Venoms House
Each of the Poison Clan is alternatively referred to as either their venom style code name, or as their number in regard to the order of being taught by the master (except Yan, who refers to himself in one scene as "number 4" implying that the master may have begun teaching a new set of 5 venoms). Among fans, he is known as "Hybrid Venom," as his training contains a little bit of each of the five styles, but it is incomplete, and he must align with one of the venoms to stand a chance against any of the others.
Number 1: Centipede - Wriggly and quick, this style is a nice blend of defensive and offensive posturing. The strikes are so fast that it is almost as if he has a hundred arms and legs. The weakness of this style as revealed by Yan Tieh (told by his master) is to attack both the opponent's upper and lower body in a simultaneous assault.
Number 2: Snake - On one hand: the mouth, venomous fangs emulated in precise finger motor control, designated to aim for the target's vulnerable spots with pin-point accuracy. On the other: the stinging whip of a rattling tail. Masters of this ability can even fight extremely well while lying on their back from the floor. The weakness of this style as revealed by Yan Tieh (told by his master) is to stop the "head" and "tail" (the opponent's two arms) from combining, as neither the head nor tail can function well individually. This usually meant pinning the two limbs, at an angle, as far away from each other as possible.
Number 3: Scorpion - The scorpion represents a double threat. Kicks from the Scorpion style are just like the stinging tail of the namesake. When delivered by a master, a single kick can paralyse or even kill, let alone the strong pincer-style attack of the arms to contend with. The weakness in this style is not clearly revealed as Yan Tieh is cut off from his explanation but one can assume (by watching The Scorpion in his bout with Yan Tieh and The Lizard) that it would be to stay out of reach of The Scorpion's damaging kicks and make him come to you.
Number 4: Lizard - An emphasis on speed and gravity, the Lizard style is best known for the ability to walk on walls, and can fight with ease from such positions, even maneuver in such a way that can rebound off such sources to both dodge assaults as well as strengthen own attacks.
Number 5: Toad - This is a primarily defensive pose. The Toad is invulnerable to just about any form of damage, including blades and puncture. They can even bend solid metal. The weakness of this style is that any master of the Toad style has a "weak spot" that when punctured, drains the user's Toad style benefits (most notably the iron skin.) Number 5's weak spot were his ears as shown in his fight with The Snake, when The Scorpion secretly struck his ears with his darts. Some thought the way to discover the weak spot in one's Toad style is to use an iron maiden. But when Number 5 was first placed in the iron maiden, he was impervious to the needles. The iron maiden's needles only penetrated the Toad after the Scorpion and Snake exploited his weak spot, the ears, with darts and a snake strike.
The film received a DVD release by the Weinstein Company's Asian label, Dragon Dynasty, on 18 August 2009.