Sheppard was born in Jacksonville, Florida in 1981. He attended William M. Raines High School in Jacksonville, where he was an all-state selection and USA Today All-American at defensive back for the Raines Vikings high school football team. Sheppard had eighteen interceptions in twenty-nine games as a junior and senior, and led the Vikings to an undefeated season and a state championship in 1998. In 2007, eight years after he graduated from high school, the Florida High School Athletic Association (FHSAA) recognized Sheppard as one of the "100 Greatest Players of the First 100 Years" of Florida high school football.
Sheppard accepted an athletic scholarship to attend the University of Florida in Gainesville, Florida, where he played for coach Steve Spurrier's Florida Gators football team from 1999 to 2001. He was a first-team All-American as a sophomore in 2000, and a first-team All-Southeastern Conference (SEC) selection in 2000 and 2001. In his three-season college career, he started twenty-two games, recorded eight interceptions, had eighty-seven tackles, and returned twenty-seven kickoffs for 472 yards (an average of 22.5 yards per return). Sheppard declared himself eligible for the NFL Draft after his junior year.
In one of a series of articles published by The Gainesville Sun in 2006, he was ranked as No. 44 among the 100 greatest Gators from the first 100 years of Florida football.
In the 2002 NFL Draft, Sheppard was selected in the first round (twenty-sixth pick overall) by the Philadelphia Eagles.
In 2004 Sheppard had five interceptions, including two returned for touchdowns. He was named Defensive Player of the Month for the month of November after returning two interceptions for touchdowns. Sheppard was selected to his first Pro Bowl in 2004, and he was also named first team All-Pro for his first and only year.
2005 was the first of three injury filled seasons for Sheppard. He missed six games and finished with three interceptions.
On October 8, 2006, Lito became the first player in NFL history to have two interception returns of more than 100 yards. Both returns came against the Dallas Cowboys (2004 and 2006). The most recent return sealed a 38-24 win over the Cowboys and secured 1st place in the division for the Eagles.
In the Eagles Wild Card playoff game on January 7 against the New York Giants, Sheppard dislocated his elbow. He missed the next playoff game against the Saints, which the Eagles lost 27-24.
In a 2007 game against the Green Bay Packers Sheppard suffered an injury. Sheppard went through another injury-filled season and finished with two interceptions.
In the 2008 offseason, the Philadelphia Eagles signed former New England Patriots cornerback Asante Samuel, which fueled speculation that Sheppard was available via trade. Sheppard changed agents to Drew Rosenhaus soon afterwards.
During the 2008 season, Sheppard saw much reduced action due to good performances by starting corners Asante Samuel and Sheldon Brown.
Sheppard was traded to the New York Jets on February 28, 2009, for a fifth round pick in the 2009 NFL Draft and a conditional pick in the 2010 NFL Draft. The Jets restructured Sheppards' contract, adding one year and "new" money to the contract in 2010. He was released on March 4, 2010.
Sheppard signed a one-year, $2 million contract with the Minnesota Vikings on April 21, 2010. He became a free agent following the 2010 season.
Sheppard was signed by the Oakland Raiders on August 26, 2011, released during the final cuts on September 3, and then re-signed by the team on October 31. During the remainder of the 2011 season, he played in nine games and started seven of them. He became a free agent after the season.
KeyGP: games played
COMB: combined tackles
TOTAL: total tackles
AST: assisted tackles
FF: forced fumbles
FR: fumble recoveries
IR YDS: interception return yards
AVG IR: average interception return
LNG: longest interception return
TD: interceptions returned for touchdown
PD: passes defensed