With a population of about 134 million people distributed among 389 ethnic groups, Nigeria is a country of great diversity. The socio-cultural factors or practices in Nigeria that may be related to HIV/AIDS transmission are legion. These include the patriarchal family and gender differentiation, early marriage, polygyny, marital instability and remarriage, domestic violence, prostitution, scarification and other skin piercing practices, incision or cutting operations including circumcision, and all sorts of culturally imposed traditions and norms that discriminate against women. The paper discusses these phenomena with respect to HIV transmission and suggests imminent changes and social re-engineering that are essential in the era of HIV/AIDS.