Through interviews, we examined explanatory frameworks of living with HIV infection among 50 HIV-positive individuals (23 women, 27 men) receiving care at a non-governmental organization in Chennai, India. Results were analysed according to three sets of issues, all of which were found to differ by gender: causal beliefs about HIV, impact of HIV, and care/treatment of HIV. HIV-positive participants attributed their infection to biological, moral and social causes, and the physical, financial and relationship dimensions of their lives were impacted upon by the infection. Furthermore, HIV-related stigma evoked fears about isolation and discrimination. Regarding care/treatment, men were most usually first initiated into the healthcare system while women often entered as a consequence of their partner's condition. Non-adherence to medication was reported by 32% of the participants due to financial constraints or side-effects. Although all participants were hopeful about a cure for HIV, women were less positive than men about treatment. Results highlight the importance of a gender-sensitive approach to HIV care, nuanced to accommodate an individual's gender, marital status and social background.