Immunosuppression remains the mainstay of therapy for successful outcomes after lung transplantation. The need for optimal immunosuppression became evident to maintain long-term graft survival and to navigate the delicate balance between infection and rejection. Over the past two decades, immunosuppression for solid organ transplantation has evolved to target multiple immune pathways with the hope of decreasing both acute and chronic allograft rejection. Although current maintenance therapy after lung transplantation typically includes a calcineurin inhibitor, antimetabolite and corticosteroid therapy, newer therapies including induction therapy with biological agents, mTOR inhibitors, and salvage therapies including photopheresis and total lymphoid irradiation have emerged as alternate therapeutic options. This review will discuss both the current immunosuppressive medications that are used as well as different therapeutic combinations that are currently employed. In addition, we will discuss the current literature regarding the efficacy of these agents in lung transplantation.