Over the last 40 years, the dynamics of hepatitis C virus (HCV) infection in drug users has been affected by the illicit drug market, the health environment including the devastating impact of the HIV/AIDS epidemic which erupted in the 1980s, and the diffusion of substitution treatment beginning in 1995. The purpose of this literature review is to present the dynamics of HCV infection in drug users in France over the last 40 years. Two prevalence studies of HCV infection in the general population were conducted by the French Institute for Public Health Surveillance in 1994 and 2004 and were the touchstone data sources for this analysis. Hypotheses constructed from the findings of these two studies were examined in light of results reported by multicentre prevalence and incidence studies in drug-user populations. The incidence of HCV infection in drug users in France reached a peak in the late 1980s or early 1990s after a lengthy period of epidemic expansion. Implementation of a risk reduction policy enabled a very significant reduction in the incidence of HCV infection in drug users over the last 20 years, leading to incidence figures which are now 10-15% of the 1990 estimate.