Reactivation of hepatitis B virus (HBV) infection is well documented complication of cytotoxic or immunosuppressive therapy in asymptomatic HBV carriers. Its clinical manifestation include fulminant hepatitis which may result in fatal liver failure. With the more widespread use of chemotherapy and hematopoietic stem cell transplantation, the problem of delivering potentially harmful treatment to HBV carriers is becoming increasingly frequent. Until recently the management of HBV reactivation has been mainly supportive. With the introduction of lamivudine, a highly effective nucleoside analogue against HBV with an excellent toxicity profile has become available. However, in light of the possibility that its prolonged use may foster the emergence of mutant lamivudine-resistant HBV strain, caution is required before recommending its widespread use. The present review briefly addresses the epidemiological, pathogenetic and clinical aspects of HBV reactivation as well the predisposing factors to its development. The results obtained with lamivudine both as treatment and as prophylaxis of hepatic flares are analysed in detail in order to provide a rational basis for clinical decisions before treating HBV carriers with chemotherapy.