In contrast to the role of TRAIL, which, to our current knowledge, seems limited in preventing autoimmunity through its action on different T cells subtypes, the contribution of the FasL/Fas system in autoimmune disease development reaches a high level of complexity, depending on the multiplicity of the cellular subsets involved and the multiplicity of functions activated by Fas triggering (Figure 1). Here, FAS is linked to Autoimmunity.