Vaginal microbicides are topical compounds that are expected to protect women against vaginal transmission of HIV and other sexually transmitted pathogens. A large number of compounds are being evaluated as possible microbicides. Considering the spread of the HIV epidemic among women in India, clinical trials on microbicides starting from the Phase I safety and acceptability studies to Phase III efficacy trials are important. Conducting efficacy trials is a major endeavour and this review discusses challenges and issues and the preparatory steps to make such efficacy trials possible in India.