He made his film debut in 1988 with a supporting role in the comedy Kamikazen: Last Night in Milan, directed by Gabriele Salvatores.

Since then, he has collaborated multiple times with Salvatores, as well as more prominently with other Italian directors such as Nanni Moretti, Daniele Luchetti, and Carlo Mazzacurati.

During his career, Orlando has been nominated seven times to the David di Donatello Award for Best Actor, winning it in 2006 for his role in Moretti's The Caiman.

[1] In 2008 he won the Volpi Cup for Best Actor at the Venice Film Festival for his role in Giovanna's Father.

On stage, Orlando most notably directed in 1988 two plays by Peppino De Filippo, Don Rafelo 'o trombone and Cupido scherza e spazza, while in 2008 he acted in Roberto Paci Dalò's L'assedio delle ceneri.