In 1990, he recorded his debut album During Christine's Sleep as frontman of Afterhours. In 1992, they recorded Mio Fratello è Figlio Unico - featured in the Rino Gaetano tribute album, produced by the Arezzo Wave festival - and in 1995 Germi, their first album completely in Italian.

In 1997 Hai paura del buio? was released, and in the meanwhile Manuel Agnelli also started his career as a singer, songwriter, producer of the group, and also producer of other bands, working at Cristina Donà's debut album Tregua.

Between 1997 and 1999 he collaborated with the groups Pitch, Scisma, Massimo Volume, and La Crus. In May 1999 Non è per sempre was released, in 2001 Siam tre piccoli porcellin, and in 2002 Quello che non c'è; in 2001 he organized the Tora! Tora! Festival, of which he still is director.

Due to his will to collaborate with other musicians - which makes him a unique artist in the Italian music scene - the 2004 Afterhours tour featured Greg Dulli's Twilight Singer: this collaboration also marked their international debut with Ballads for Little Hyenas.

After a second American tour, that begun with their concert at Austin's South by Southwest Festival, in 2008 they released their album I Milanesi Ammazzano il Sabato.