Body weight changes in HCV patients on interferon therapy are well documented. However, the underlying mechanism involved in these changes is poorly understood and rarely reported. The main objectives of this review are to 1) discuss changes in body weight and other compartments of body composition, particularly, body fat, and 2) to discuss the underlying mechanism for these changes. The literature review suggests weight loss (12-29%) as a function of interferon therapy is common, affecting up to 90% of HCV patients. Whilst, loss in weight means proportionate loss in other body compartments (lean body mass and body fat, in particular) data on changes in segmented body composition are fragmentary. The possible mechanisms underlying weight loss or changes in other body composition have been reported and these include suppressed appetite due to induction of TNF by IFN, a decrease in serum leptin level, and importantly mitochondrial damage induced by the therapy. It is, therefore, suggested that close monitoring of chronic HCV patients receiving PEG-IFN and/or ribavirin for side effects of these drugs, particularly those related to weight loss, is vitally important from clinical point of view.