The HIV epidemic in China started among intravenous drug users in the late 1980s. The second wave of the epidemic was caused by an outbreak in the paid plasma donors in central China in the mid-1990s. Sexually transmitted HIV cases have steadily increased and comprised more than half the reported HIV/AIDS infections since 2007. In the last 5 years, there has been a sharp increase of HIV infection in men who have sex with men. The HIV epidemic in China has expanded from high-risk groups to the general population and from rural regions to urban areas. This brief article discusses the history of HIV epidemics in China and the challenges facing the current AIDS control efforts in the country. It explains that only scientific approaches can sustain the national AIDS control programs and introduce the type of research needed to address those challenges. The selected research areas include molecular epidemiology, drug resistance surveillance, and the Chinese HIV vaccine research.