Numerous studies have shown that statin therapy initiated early after heart transplantation improves the short- and long-term prognosis, leading to a reduction in the incidence of cardiac allograft vasculopathy (CAV), acute rejection episodes and significantly lowers the incidence of cancer in this patient population. The molecular mechanisms responsible for the beneficial effects of statins in patients after heart transplantation are complex; the effectiveness of statins is associated not only with their hypolipemic action, but also with their pleiotropic properties. Statins have been shown to exert protective and therapeutic effects against cancer because they act as antiproliferative agents, promoting apoptosis and inhibiting angiogenesis. Moreover, they reduce the number of circulating monocytes, which inhibits the secretion of proinflammatory cytokines, growth factors, adhesion molecules, chemokines, and matrix metalloproteinases, preventing chronic rejection and CAV. For these reasons, statins should be used as part of standard therapy in patients after heart transplantation.