Medication adherence is a complex behaviour with multiple determinants. Understanding the barriers and facilitators of adherence is invaluable for programme improvement, which assists the foundation of adherence intervention strategies. A qualitative study was conducted in six selected hospitals of Addis Ababa in 2008, to explore barriers and facilitators to antiretroviral medication adherence among HIV-infected paediatric patients. Twelve caregivers of adherent and non-adherent children and 14 key informants in five hospitals were included in the study. The findings revealed that over-dosage (heavy pill burden), fear of stigma and discrimination, cost and access to transportation, lack of understanding of the benefit of taking the medication, economic problems in the household, and lack of nutritional support were the barriers to adherence to HAART. The presence of mobile/wall alarm, the presence of follow-up counselling, improved health of the child, ART clinic setups, and disclosure of HIV serostatus were among the facilitators. This study indicated that paediatric adherence to antiretroviral therapy faces a huge challenge. It suggests the provision of income-generating schemes to caregivers for assisting HIV-infected children. Health care providers should address proper usage of medication reminders.