Any meaningful conversation regarding the intricate connection between religion, health, well-being, and development in Africa is inherently incomplete if it skirts the influence of the Bible, which remains a foundational text within many communities. Drawing examples from various African countries, this chapter interrogates the role of the Bible in promoting health, well-being, and development in Africa, particularly in the context of the HIV epidemic. Through a critical analysis of both supportive and detrimental influences of the Bible against the challenging realities of the epidemic, the chapter demonstrates how responsible interpretations championed by African biblical scholars and theologians are a powerful tool for achieving the kind of progressive and healthy society enunciated and anticipated in the broader framework of the 2030 Agenda for Sustainable Development. Employing the concept of Religion as a Social Determinant of Health as its primary theoretical lens, the chapter demonstrates how biblical teachings have directly and indirectly impacted health behaviors and community dynamics, ultimately affecting the spread and management of HIV/AIDS. To achieve this, the chapter reflects on academic representations of how the Bible has been read in response to the HIV epidemic in Africa. The chapter also reflects on the lived experiences of Canon Gideon Byamugisha, an Anglican priest and theologian who has championed the quest for positively interpreting the Bible in the context of HIV/AIDS. Ultimately, the chapter advocates for a holistic approach that leverages biblical resources to foster resilience, support vulnerable populations, and contribute to sustainable health and well-being across the African continent.