Heightened interest in sex and gender differences in HIV warrant a review of the status of current understanding of their determinants and progress in addressing them.The proportion of women among people living with HIV continues to increase in most countries; however, women are proportionately more likely to be on antiretroviral treatment than are men. Inadequate representation of women in clinical trials is compounding the dearth of information on sex-based differences in response to life prolonging antiretroviral medication. Progress in addressing gender inequalities and inequities, though incremental, is too slow to reach Millennium Development Goal 6 of halting and reversing the HIV epidemic by 2015. Structural determinants, such as food insufficiency, poverty, decreased access to credit, and inequitable inheritance practices, continue to act with social gender norms to shape the increased risk of exposure to HIV that women and adolescent girls face in many settings.Special measures should be taken to overcome barriers and facilitate enrolment and retention of women in biomedical HIV prevention and treatment trials. Law reform, economic empowerment, gender transformative work, and political mobilization are needed if women and men are to share the power, influence, rights, responsibilities, and opportunities that can create resilience to HIV.