Introduction: The goal of antiviral therapy in patients with chronic hepatitis C is to slow or halt the progression of fibrosis and prevent the development of cirrhosis. Accordingly, antiviral treatment is proposed for a large population of patients with chronic hepatitis. Areas covered: The standard-of-care for chronic hepatitis C is the combination of pegylated IFN (PEG-IFN) and ribavirin. The use of these drugs has been correlated with a range of adverse effects, including influenza-like symptoms, hematological changes and neuropsychiatric disturbances. The effects of these adverse events associated with PEG-IFN therapy are manifold and are a major reason why patients decline or stop therapy. This review addresses the screening for adverse event risk factors and guides the patient to success with adherence strategies. Expert opinion: Knowledge of the side effects correlated with PEG-IFN is very relevant for clinicians because it can allow them to arrange the best methods for treating these effects and avoid the discontinuation of antiviral treatment. Moreover, the use of new antiviral drugs will considerably shorten treatment periods reducing many of the above-described side effects and, thus, increase adherence to scheduled therapy.