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Cyclosporine A (CsA) is a well-known immunosuppressive agent that gained considerable importance in transplant medicine in the late 1970s due to its selective and reversible inhibition of T-lymphocytes. While CsA has been widely used to prevent graft rejection in patients undergoing organ transplant it was also used to treat several systemic and local autoimmune disorders. Currently, the neuro- and cardio-protective effects of CsA (CiCloMulsion®; NeuroSTAT®) are being tested in phase II and III trials respectively and NeuroSTAT® received orphan drug status from US FDA and Europe in 2010. The reformulation strategies focused on developing Cremophor® EL free formulations and address variable bioavailability and toxicity issues of CsA. This review is an attempt to highlight the progress made so far and the room available for further improvements to realize the maximum benefits of CsA.