Gender has long been recognized as being key to understanding and addressing HIV and AIDS. Gender roles and relations that structure and legitimate women’s subordination and simultaneously foster models of masculinity that justify and reproduce men’s dominance over women exacerbate the spread and impact of the epidemic. Notions of masculinity prevalent in many parts of the world that equate being a man with dominance over women, sexual conquest and risk-taking are associated with less condom use, more sexually transmitted infections, more partners, including more casual partners, more frequent sex, more abuse of alcohol and more transactional sex. They also contribute to men accessing treatment later than women and at greater cost to public health systems. The imperative of addressing the gender dimensions of AIDS has been clearly and repeatedly articulated. Many interventions have been shown to be effective in addressing gender-related risks and vulnerabilities including programmes designed to reach and engage men, improve women’s legal and economic position, integrate gender-based violence prevention into HIV services, and increase girls’ access to secondary and tertiary education. Despite this, the political will to act has been sorely lacking and not nearly enough has been done to hold governments and multilateral institutions to account. This paper argues that we can no longer simply pay lip service to the urgent need to act on what we know about gender and AIDS. Simply put, it is time to act.