Grandparents throughout sub-Saharan Africa have shown immense courage and fortitude in providing care and support for AIDS-affected children. However, growing old comes with a number of challenges which can compromise the quality of care and support they are able to provide, particularly for children infected by HIV and enrolled on antiretroviral therapy (ART) programmes. For ART to be effective, and for infected children not to develop drug-resistance, a complex treatment regimen must be followed. Drawing on the perspectives of 25 nurses and eight grandparents of HIV-infected children in Manicaland, eastern Zimbabwe, we explore some of the challenges faced by grandparents in sustaining children’s adherence to ART. These challenges, serving as barriers to paediatric ART, are poverty, immobility, deteriorating memory and poor comprehension of complex treatments. Although older HIV-infected children were found to play an active role in sustaining the adherence to their programme of treatment by contributing to income and food generating activities and reminding their guardians about check-ups and drug administration, such contribution was not available from younger children. There is therefore an urgent need to develop ART services that both take into consideration the needs of elderly guardians and acknowledge and enhance the agency of older children as active and responsible contributors to ART adherence.