Internationally, there has been a recent resurgence of interest in HIV and AIDS-related stigma and discrimination, triggered at least in part by growing recognition that negative social responses to the epidemic remain pervasive even in seriously affected communities. Yet, rarely are existing notions of stigma and discrimination interrogated for their conceptual adequacy and their usefulness in leading to the design of effective programmes and interventions. Taking as its starting point, the classic formulation of stigma as a 'significantly discrediting' attribute, but moving beyond this to conceptualize stigma and stigmatization as intimately linked to the reproduction of social difference, this paper offers a new framework by which to understand HIV and AIDS-related stigma and its effects. It so doing, it highlights the manner in which stigma feeds upon, strengthens and reproduces existing inequalities of class, race, gender and sexuality. It highlights the limitations of individualistic modes of stigma alleviation and calls instead for new programmatic approaches in which the resistance of stigmatized individuals and communities is utilized as a resource for social change.