[3] After starting out at Roma, he went on to compete in Serie A for 12 seasons, spending most of his time at Udinese and Juventus and amassing totals of 251 games and 31 goals, winning four consecutive national championships with the latter club.

[6][7] It was reported that Roma chairman Franco Sensi owed his Palermo counterpart Maurizio Zamparini money, and both Pepe and Cesare Bovo were sold to the latter at an un-economic price to settle the debt,[8] but the former denied this, stating the transfers were totally transparent.

[13] As they were again intent on signing youngsters he featured sparingly, moving to Cagliari Calcio in a temporary deal in July 2006 as the former club had just recalled Gyan Asamoah who shined at that year's FIFA World Cup; the latter also purchased 50% of his registration rights from Palermo for €1.5million.

In 2011–12, Pepe formed an efficient right-wing partnership with newly signed Stephan Lichtsteiner, contributing with four of his six league goals and two assists after the first ten fixtures.

On 11 September 2011, in Juventus's opening match of the season at the club's new stadium, he scored the second goal in an eventual 4–1 home win over Parma.

[24][25][26][27] Pepe was operated on 27 February 2013, and after a few matches with the youth squad[28] he returned to the pitch on 18 December, coming on as an 81st-minute substitute of a 3–0 win over U.S. Avellino 1912 in the Coppa Italia.

[37] In spite of a first poor year in the Serie A, Pepe was selected by the Italian under-21 team to the 2006 UEFA European Championship,[38] but he did not play in any games in Portugal in an eventual group stage exit.

[39] He made his debut with the senior side on 11 October 2008, under manager Marcello Lippi, in a 0–0 away draw against Bulgaria for the 2010 FIFA World Cup qualifiers.

Bari 1908 in May 2010 during his time with Udinese, and faced a potential one-year ban if found guilty; he denied any wrongdoing, however,[50] and he was later acquitted of all charges in August 2012.