Despite the growing interest in social entrepreneurship research in the social work literature, very little research examines how social entrepreneurs tackle social work challenges in the HIV/AIDS sector. Consequently, we lack research on how social entrepreneurship might contribute to social work’s domain of healthcare. In this article, we employ grounded theory research to study how a group of social entrepreneurs (N = 58) selected as Fellows by Ashoka, one of the world’s most influential social entrepreneurship support organizations, solve HIV/AIDS problems. This article identifies four major interventions that social entrepreneurs employed in tackling HIV/AIDS problems: relational, service, economic, and policy. We analyzed these four primary interventions and classified them into a typology based on (1) locus of change (institutional-oriented or macro social work vs agent-oriented or micro social work), (2) resources used (material/utilitarian vs symbolic/normative), and (3) client–social enterprise relations (client as recipient vs client as co-creator). This article contributes to social work research by demonstrating the possibility of integrating multilevel (e.g. micro and macro) and multidimensional (e.g. service, economic, and policy) interventions in addressing HIV/AIDS problems. It also suggests avenues for future research to lessen the gap between social work and social entrepreneurship research so as to advance social work research.