Over the last two decades there has been a significant increase in the number and types of immunosuppressive agents that have been available to clinicians. The protocols for immunosuppression used in liver transplantation have been derived historically from those in renal transplantation. During the last decade there has been a shift in the use of immunosuppression, with the introduction of interleukin (IL)-2 receptor antagonists in place of anti-lymphocyte preparations, substitution of tacrolimus for cyclosporin and mycophenolate for azathioprine. The use of corticosteroids has been reduced. For a variety of reasons, these changes have not always been made on the basis of properly randomized studies. The place of newer agents, such as sirolimus and leflunomide derivatives and of the microbiological agents, is unclear. In this review, we outline briefly the mechanism of action of drugs and suggest possible approaches to the management of the liver allograft recipient, suggesting how treatment could be adjusted according to the indication for transplantation as well as the individual's comorbidities.