Grounded in the social constructivism tradition, this study examined the role of communication in the glocalization and acculturation of HIV/AIDS by a section of sexually active Ugandans then living in Rakai district during the advent of the epidemic in 1982. Sixty-four women and men participated in ten focus group discussions in Rakai and Kampala districts. Five themes emerged from the data highlighting how individuals and communities made sense of the epidemic, the omnipresence of death, how they understood the HIV/AIDS campaign, and how they are currently coping with its backlash. The study concludes that HIV/AIDS is socially constructed and can be understood better from local perspectives rather than from a globalized view. The study emphasizes the integration of cultural idiosyncrasies in any health communication campaigns to realize behavioral change.