The adverse effects of antiviral drugs are dose dependent and often reversible. The major side effects include influenza-like symptoms, hematologic abnormalities and neuropsychiatric symptoms. The influenza-like syndrome can be prevented by paracetamol taken at the time of injection. Psychiatric adverse effects range from irritability to severe depressive syndrome. Antidepressants such as selective serotonin reuptake inhibitors may be useful. Adverse hematologic effects can occur very early during treatment. The platelet count often stabilizes rapidly, but neutropenia can deteriorate throughout the treatment. In selected patients, treatment with hematopoietic growth factor (filgrastim) may be useful. Ribavirin therapy may result in a dose-dependent reversible intravascular hemolytic anemia in 10% of patients. Therapy with erythropoietin for ribavirin induced anemia can be useful; however, are insufficient data to recommend its routine use in all patients. Interferon and ribavirin are contraindicated in pregnancy. Contraception must be continued for 4 months (women) and 7 months (men) after ribavirin cessation. Lactic acidosis may be a rare complication of combination therapy in patients undergoing therapy for HIV and HCV. Any sign of mitochondrial DNA depletion syndrome calls for blood lactate measurement and, possibly, a modification of antiretroviral treatment. Lamivudine is well tolerated but the emergence of lamivudine-resistant (YMDD) HBV mutants is associated with the loss of clinical response. Adefovir, entecavir, telbivudin and tenofovir effectively suppress lamivudine-resistant HCV in chronic hepatitis B.