Triggering the CD95/APO-1/Fas receptor by CD95-L induces the assembly of the death-inducing signaling complex (DISC), which permits initiator caspases activation and progression of a signaling cascade that culminates in cellular apoptosis. Despite the CD95 receptor does not exhibit any kinase activity by itself, phosphorylation/dephosphorylation events seem important to regulate many aspects of CD95-mediated apoptosis. Here, we try to highlight particularly the importance of protein phosphatases in the modulation of the CD95 system.