There has been considerable interest in the individualization of immunosuppressive regimens in an attempt to avoid side effects and improve long-term outcomes. Most available studies have addressed steroid and calcineurin inhibitor minimization in an attempt to prevent the development of chronic allograft dysfunction and cardiovascular mortality. Herein, we evaluate the available evidence for incorporation of these novel strategies in standard clinical care of kidney transplant recipients. Protocol biopsies, pharmacogenetics, and other assays have been developed to guide tailoring of immunosuppression; however, although promising results have been obtained, trials showing their ability to improve long-term outcome are lacking and urgently needed.