Transplant medicine has seen many innovations over past decades and continues to evolve into the 21st century. Newer immunosuppressive strategies in renal transplantation are associated with better patient and graft survival rates; however, the adverse toxicities and long-term side effects associated with these agents present a number of challenges. Certain immunosuppressants are commonly used in dermatologic disorders, however, dermatologists may be less familiar with the clinical efficacy, side-effect profile, and dosage of newer immunosuppressive agents. A knowledge of the molecular and cellular mechanisms of action of these agents gives us a better understanding of how these agents contribute to the cutaneous and mucosal complications frequently seen post-transplant. With the advent of new immunosuppressive therapies and different treatment regimens, there is an increasing need for a multidisciplinary approach to balancing the risks and benefits of these medications to the individual transplant recipient. This review will highlight the different immunosuppressive agents and their effect on the skin while focusing on the evidence base to support the commonly used immunosuppressive regimes, newer protocols aimed at achieving maximum graft survival with minimal side effects, and important drug interactions with which all dermatologists should be familiar.