Sub-Saharan Africa is facing a crisis in human health resources due to a critical shortage of health workers. The shortage is compounded by a high burden of infectious diseases; emigration of trained professionals; difficult working conditions and low motivation. In particular, the burden of HIV/AIDS has led to the concept of task shifting being increasingly promoted as a way of rapidly expanding human resource capacity. This refers to the delegation of medical and health service responsibilities from higher to lower cadres of health staff, in some cases non-professionals. This paper, drawing on Médecins Sans Frontières’ experience of scaling-up antiretroviral treatment in three sub-Saharan African countries (Malawi, South Africa and Lesotho) and supplemented by a review of the literature, highlights the main opportunities and challenges posed by task shifting and proposes specific actions to tackle the challenges. The opportunities include: increasing access to life-saving treatment; improving the workforce skills mix and health-system efficiency; enhancing the role of the community; cost advantages and reducing attrition and international ‘brain drain’. The challenges include: maintaining quality and safety; addressing professional and institutional resistance; sustaining motivation and performance and preventing deaths of health workers from HIV/AIDS. Task shifting should not undermine the primary objective of improving patient benefits and public health outcomes