In the recent years, studies of hepatitis B (HBV) and hepatitis C virus (HCV) dynamics have drawn great attention as they provide insight into the process of virus elimination/production and of infected cells decay during antiviral treatment. Estimates of viral dynamic parameters may be used to determine the lifetime of HCV/HBV virions and of infected cells, to estimate how long patients need to be treated and to evaluate antiviral therapies. The implementation of viral dynamics studies is difficult because they involve an intensive blood-sampling schedule and subsequent viral load quantification. In the majority of these studies, a model proposed by Neumann et al. (Science 1998; 282:103–107) is used under various assumptions, such as ignoring the delay in initial viral load decay, assuming time-constant treatment efficacy in reducing virion production and/or complete blocking of new infections, etc. However, only recently the effect of some of these assumptions on the estimated parameters has been evaluated. In this paper we provide a detailed review of the model, its underlying assumptions as well as the assumptions usually made by researchers during the design and analysis of viral dynamics studies. Then, we investigate the effect of these assumptions on the estimated parameters using simulations and draw useful conclusions concerning the analysis of these studies. Real data examples from a clinical trial on hepatitis B are provided as illustrations. Copyright © 2008 John Wiley & Sons, Ltd.