Proteins of the cyclophilin family display two intriguing properties. On the one hand, they are the intracellular receptors for the immunosuppressive drug cyclosporin A (CsA); on the other hand, they function in vitro as enzymes that catalyse slow steps in protein folding. A dissection of the role of CsA in mediating immunosuppression, together with recent studies on the biology of cyclophilins in the absence of this ligand, is providing fundamental insight into the cellular function of this protein family.