Caregiving for people living with HIV/AIDS (PLWHAs) reportedly affects the physical, mental, and socioeconomic well-being of family and volunteer caregivers. This study uses the PEN-3 cultural model to examine the positive, existential (unique), or negative roles and expectations that influence HIV and AIDS caregiving among home-based caregivers (HBCs) in Limpopo, South Africa. Data from 41 women who participated in four focus group discussions held in Limpopo provides a deeper understanding of culture in providing care and support to PLWHAs. Using the cultural empowerment domain of PEN-3, our analyses revealed the following themes: perceptions associated with HIV/AIDS caregiving, HBCs assuming the roles of family, and voicelessness of HBCs due to the lack of support. The findings highlight the resilience of HBCs in South Africa in responding to the stigmatized disease of HIV/AIDS in the context of cultural expectation of caring for the sick.