Caspases are a family of aspartate-specific cysteine proteases that have been well characterized for their function in apoptosis signaling. Caspase-8 is implicated as an initiator caspase in death receptor-induced signaling to apoptosis and has been studied most extensively for its role in CD95-induced cell death. CD95 stimulation induces the binding of caspase-8 to a death-inducing signaling complex, leading to its autocatalytic cleavage and the formation of a caspase-8 homodimer, which is subsequently released into the cytosol where it further mediates the apoptotic signaling cascade. Over the past few years, however, several non-apoptotic functions for caspase-8 have been described, indicating that this protease plays a much more diverse role than previously assumed. Here we review the role of caspase-8 in embryonic development, monocyte differentiation, T and B cell proliferation, and the activation of NF-kappaB.