In the race's final week, Contador faced stern challenges from Riccò and defending Giro champion Danilo Di Luca.

In August 2008, mountains classification winner Emanuele Sella was announced to have tested positive for methoxy polyethylene glycol-epoetin beta (better known as Mircera, an erythropoietin derivative) at an out-of-competition control held by the Union Cycliste Internationale (UCI).

Defending champion Danilo Di Luca had faced potential bans which would have kept him out of the race, after investigations into his involvement with the Oil for Drugs scandal and an irregular doping test given after stage 17 of the 2007 Giro d'Italia, either of which could have resulted in a two-year suspension.

[10] Though he was suspended for three months because of Oil for Drugs,[11] he was cleared by the Italian National Olympic Committee of any wrongdoing in the 2007 Giro,[12] and was thus permitted to start.

[14] Both Di Luca and Contador had strong domestiques (support riders) by their sides, with Di Luca joined by two-time Giro d'Italia champion Paolo Savoldelli, Gabriele Bosisio, and Alessandro Spezialetti, and Contador by Leipheimer and Klöden.

[15] Other riders named as overall contenders included Denis Menchov,[14] Gilberto Simoni, Vincenzo Nibali, Riccardo Riccò, Mauricio Soler, Marzio Bruseghin, Emanuele Sella, Evgeni Petrov, Franco Pellizotti, and Juan Manuel Gárate.

[14] Italian sprinter Alessandro Petacchi, who had notably won nine stages in the 2004 race, did not plan to enter this Giro because of bouts with influenza and bronchitis which hindered his training.

[15][17] He was later suspended from the sport, and his contract with Team Milram terminated,[18] as a result of his controversial doping case from the 2007 Giro.

[17] Sprinters identified as being favorites in the bunch finishes that the Giro would offer included Alexandre Usov, Dimitry Muravyev, Enrico Gasparotto, Maximiliano Richeze, Robert Förster, Mark Cavendish, André Greipel, Daniele Bennati, Paolo Bettini, Graeme Brown, Robbie McEwen, Julian Dean, Erik Zabel, and Alberto Loddo.

[13] Richeze was withdrawn by his team CSF Group–Navigare the day before the race began after a positive doping test, though he would later be cleared of any wrongdoing.

[19] His name remained on the start list, and he was not replaced, meaning CSF Group–Navigare entered the race with only eight riders instead of the customary nine.

[20] The race began for the second year in succession with a team time trial on one of Italy's islands, in this case Sicily (in 2007 it had been Sardinia).

He lost it to Franco Pellizotti, who finished sufficiently ahead of Vande Velde on the stage to take a lead of a single second in the overall classification.

[31] Pellizotti retained the race lead for the next three days, as those stages were flat and were contested by sprinters, with the overall favorites finishing together with the peloton in each.

[34] Contador faced repeated challenges from Riccardo Riccò and Danilo Di Luca in the race's final week.

[38][42] His subsequent positive tests and confessions to the use of performance-enhancing drugs outside the Giro cast serious doubt on the legitimacy of these results, however.

He led the classification after every stage except the second and eighth, which were both won by Riccò, who thereby gained the mauve jersey for one day on two separate occasions.

None of them would return to the Giro in 2009; Gerolsteiner folded in 2008 after being unable to locate a new sponsor[58] while Euskaltel–Euskadi, Cofidis, and Française des Jeux all made it known that they did not wish to participate and were thus declined invitations.

[59] Several notable riders in the Giro were announced to have tested positive for banned performance-enhancing drugs after the race concluded.

It was announced on 5 August that Sella had tested positive for Methoxy polyethylene glycol-epoetin beta, better known as Mircera, a third-generation form of the banned blood booster erythropoietin.

An out-of-competition control was taken on 23 July, just days after positives from the 2008 Tour de France had come to light, and samples were sent to labs in Paris for analysis.

[60] Sella confessed his doping to the Italian National Olympic Committee (CONI)[61][62] and named teammate Matteo Priamo, also a stage winner in this Giro, as his supplier.

[2] Though Priamo never tested positive for anything, and though the Italian National Anti-Doping tribunal originally exonerated him,[63] the Court of Arbitration for Sport ruled, upon appeal by CONI, that he should be suspended for four years.

[64][65] Riccardo Riccò, a double stage winner and the best young rider, tested positive for Mircera during the Tour de France, and was subsequently expelled with his team Saunier Duval–Scott.

After repeated positives over the summer, including tests from Leonardo Piepoli and Bernhard Kohl at the Tour de France,[68] and Davide Rebellin and Stefan Schumacher from the 2008 Olympic Games,[69] the UCI has sought to have samples taken during the Giro retested.

In October 2009, it was announced that six to seven riders from this Giro had presumptive positives,[3] while further untestable doping involving ozone was also suspected.

[4] In total, 82 samples were retested, and the presumptive positives have been compared to values stored at an anti-doping lab in Lausanne, Switzerland.