HIV disproportionately affects women in developing countries, especially in Southern Africa. Women thus stand to benefit most from a successful HIV vaccine and must participate in trials to test appropriate, gender-specific products. Several HIV vaccine efforts are currently underway in Africa. Participation in HIV vaccine trials requires that participants not only understand the complex nature of trial procedures, but that they also have autonomous decisional capacity to enroll. Given that the risk factors inherent in women's greater vulnerability constitute an intricate mix of biological, economic and social variables, will women's very vulnerability to HIV be an obstacle to ethical participation in vaccine development? This paper addresses some of the challenges underlying the successful recruitment of women into vaccine research and makes research and policy recommendations for the ethical inclusion of women in HIV vaccine trials in Africa.