By 2020, an estimated 2.3 million South African children will be orphaned by HIV/AIDS (Actuarial Society of South Africa, 2005), but little is known about risk and protective factors for their emotional and behavioural well-being. This qualitative study explores perspectives of affected families. Orphaned children (n = 60), caregivers of orphaned children (n = 42) and social care professionals (n = 20) completed semi-structured interviews and focus groups. Participants were recruited from schools, shelters and welfare services. Findings from multiple sources indicate potential risk and protective factors in a range of dimensions, including bereavement, family functioning, social support, poverty, access to education and perceived stigma. Many factors reflected international literature on children experiencing similar stressors (e.g. non HIV/AIDS-related bereavement). However, this study also identified factors which may be specific to this group, notably stigma, abuse and peer factors. Current research is quantitatively testing associations between these identified factors and psychological outcomes.