In organ transplantation, the key tenet remains the maintenance of graft function through the induction of allograft tolerance. Immunosuppression has been the mainstay of therapy to maintain graft function and induce tolerance. Immunosuppression for lung transplant and indeed all solid organ transplantation has greatly evolved in the past decade. Although calcineurin inhibitors, corticosteroids, and azathioprine remain the foundation of immunosuppression in lung transplantation, the arsenal of effective immunosuppression is ever expanding to include biological agents and newer drugs that are directed against increasingly specific targets of the immune cascade. This review examines the characteristics of both traditional and new pharmacological agents, describes a patient-centered approach to their use following lung transplantation, and discusses the controversies surrounding immunosuppression in the lung transplant recipient.