The provision of appropriate HIV prevention, treatment, and care services for most-at-risk populations (MARP) will challenge many health care systems. For people who sell sex or inject drugs and for men who have sex with men, stigma, discrimination, and criminalization can limit access to care, inhibit service uptake, and reduce the disclosure of risks. Several models for provision of HIV services to MARP may address these issues. We discuss integrated models, stand-alone services, and hybrid models, which may be appropriate for some MARP in some settings. Both public health and human rights frameworks concur that those at greatest risk should have expanded access to services.