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, FASLG is linked to autoimmune disease.