The aim of the study was to gain a deeper understanding of the factors that influence adherence to Anti-Retroviral Treatment (ART) in a paediatric population in South India. Semi-structured interviews, guided by a questionnaire based on literature review, were undertaken with 14 primary caregivers of children with Human Immunodeficiency Virus (HIV) on ART focussing on the factors influencing adherence and non-adherence. Adherence to ART was assessed by caregiver reported adherence for the last three days. The framework approach was used for analysis of the transcribed interviews. Adherence behaviour in children taking ART was influenced by medication, child, caregiver, family and healthcare service related factors. Medication related factors such as palatability, formulation, and difficult regime were among the common reasons for non-adherence. While a supportive family appeared to contribute to adherence, some caregivers were reluctant to inform their extended family members for fear of isolation. All participants were strongly appreciative of the study centre's model of care and this had a positive effect on adherence behaviour. From the public health point of view, the respondents' reluctance to access publicly funded HIV care services is a cause for concern. Almost all caregivers were sceptical of the quality of free ART medications provided by public services, indicating an urgent need for appropriate education to alleviate their concerns. The cost of ART was reported by caregivers as an important barrier, particularly by those with low income. Most caregivers recommended wider access to free ART, availability of child-friendly medications and adherence counselling as important interventions to improve adherence. All caregivers in this study reported some difficulty in sustaining adherence in their children. Further research on improving adherence in children by tailoring interventions to the specific needs of caregivers and their families is warranted.