This paper analyses the productive activities of people living with HIV following their uptake of antiretroviral therapy (ART) in rural Uganda. It presents findings from a two-phase qualitative research project carried out in 2005-2006 with a total of 70 participants in an ART delivery programme. The thematic analysis is not focused on the economic effects of ART for individuals and their households per se, but on how their work facilitated an adjustment or 'transition' to living with HIV as a chronic condition. The term transition refers to a person's movement towards incorporating a long-term illness, treatment regimen and its various ramifications into his or her life. This transition is achieved by people taking action and making changes in various aspects of their lives and through reflective and spiritual endeavours. The narratives of work and related activities are interpreted to be adaptive strategies to achieve this transition: 'quests' to regain control, create order and to feel 'normal' again. The paper seeks to build understanding of the transition process to living with HIV as a chronic illness in a rural African setting. It also considers the factors enabling or hindering the transition process in a resource-limited setting, notably circumstances of poverty and vulnerability. Better understanding of this transition process, the adjustment challenges people face and the support needed, is important for the success of ART programmes, because people who adjust are more likely to sustain the management of their chronic condition.