Three decades into the HIV/AIDS epidemic, HIV prevention programs have been only partially effective. New prevention tools are providing new reasons for optimism. Effective use of these new tools, including the 'test-and-treat' strategy, will require considerable effort to assure that their potential for prevention is fully realized. Challenges with the test-and-treat strategy are global ones, and include retention in care and adherence to treatment. Worldwide, those with HIV infection become less adherent to antiretroviral therapy over time. Many factors contributing to retention in care and adherence to therapy differ among countries and regions of the world. HIV-infected persons receiving treatment in sub-Saharan Africa have been reported to have higher adherence rates than those receiving treatment on the North American continent; higher health literacy and perception of treatment as a social obligation may enhance adherence to treatment and retention in care. The HIV test-and-treat strategy offers a major step forward when combined with other prevention efforts; we need to consider what additional steps are needed to deliver on the promise of prevention through treatment.