Calcineurin is a Ca2+/calmodulin-regulated Ser/Thr protein phosphatase, which is involved in many physiological processes, e.g. antigen‐dependent T cell activation, differentiation of neurons, and motility of spermatocytes. Dysregulations of those processes bring calcineurin in focus of pharmacological research. Since many years, the calcineurin inhibitor Ciclosporine (CsA) is in use as immunosuppressive drug for prevention and therapy of transplantate rejections, graft-versus-host reactions and autoimmune diseases. This cumulative work describes amongst other things the identification and development of new calcineurin inhibitors. CN585 is such a candidate, which combines a low cytotoxicity, high immunosuppressive potency, and selectivity for calcineurin. Moreover, by modification of CsA in position 3, 4, 7, or 8 new compounds were obtained, which exhibit extraordinary pharmacologically properties. For example, one derivative inhibits the RNA replication in Hepatitis C virus, in another derivative the immunosuppressive effect can be switched on/off or fine tuned in a light-dependent manner. A further thioxylated derivative can be used as molecular probe for determination of binding constants.