Alemtuzumab is a monoclonal anti-CD52 antibody, which has been used extensively off label in solid organ transplantation. Its primary use has been as an induction agent at the time of organ transplantation, although there is limited experience using it to treat steroid-resistant rejection. Prolonged lymphocyte depletion can be expected following alemtuzumab treatment even with one dose of 30 mg intravenously. The nature and kinetics of lymphocyte repopulation depend on the maintenance immunosuppression being administered. In comparison with Thymoglobulin, a polyclonal depleting antibody preparation, alemtuzumab offers significant practical benefits with lower cost, fewer side effects in administration, and no specific issues with i.v. access. The risks and benefits of depleting induction agents, such as alemtuzumab, are compared with nondepleting agents, such as anti-CD25 induction therapy. While the majority of experience in solid organ transplantation has been in kidney transplantation, there is more limited experience in liver, pancreas, islet, small bowel, and lung transplantation. We herein review some of the lessons learned from clinical experience to date in solid organ transplantation using alemtuzumab as an immunosuppressant.