In the critical care setting an understanding of pharmacotherapy options and adverse effects is the key for positive patient outcomes after transplantation. Finding a balance between rejection of transplanted solid organs and complications of immunosuppressive regimens is an ongoing challenge for clinicians. Current drug therapies are able to successfully manage and reverse episodes of rejection, however, long-term sequelae remain the focus for the next generation of immunosuppressants. This article discusses current immunosuppressive agents, induction therapy, and identifies future trends.