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Tacrolimus, in spite of its good safety profile with fewer adverse effects (when treated locally) is still being used as an off-label drug to treat ocular diseases - like corneal graft-versus-host disease, conjunctivitis, uveitis and dry eye. Poor aqueous solubility, stability and permeability are the major challenges to develop tacrolimus as an ocular therapy. Currently, several novel delivery systems such as nanomicelles, proniosomes, inclusion complexes, liposomes and nano emulsion are being developed to address these challenges. This review aims to provide a detailed discussion on the various delivery strategies for tacrolimus with their advantages as well as their limitations. We have also reviewed the mechanism of action of tacrolimus in treating various ocular diseases along with its development and rising importance in replacing steroidal therapy.