There is considerable interest in the role of Fas protein as it induces apoptotic cell death when ligated by its natural ligand (FasL). Interaction between Fas and FasL is a crucial mechanism for clonal deletion and immune tolerance and privilege, control of T cell expansion during immune responses and killing by cytotoxic T lymphocytes. Loss of function of the system can block lymphocyte apoptosis and cause lymphoproliferation and autoimmunity but, when the system overfunctions, it can end to tissue injury and destruction. Recent studies have demonstrated that the Fas/FasL system is implicated in the pathogenesis of several human diseases ranging from AIDS to autoimmunity and lymphoproliferation, hepatitis, multiple sclerosis and transplant rejection. It is conceivable that modulating the activity of the Fas/fasL pathway would have clinical applications for the treatment of these patients.