The successful expansion of access to HIV testing in sub-Saharan Africa has led to hundreds of thousands of people learning that they are HIV-positive. Only a small fraction of these individuals, however, are enrolling in HIV/AIDS care and treatment programs at the time of diagnosis or at any time before they become seriously ill. As a result, most patients seek HIV/AIDS treatment long after they were eligible and with severe illness. At the same time, scale-up of services has put pressure on the ability of treatment programs to maintain care for existing patients on treatment while continuing to expand access to new patients. With increased demand and limited capacity, many patients who start care discontinue treatment. HE2RO and collaborators study retention in care by conducting epidemiologic analyses of several cohorts including the Themba Lethu Clinical HIV Treatment Cohort of over 30,000 patients—one of the largest clinical HIV treatment databases in South Africa. We also actively work on interventions to improve linkage and retention at all stages of HIV care to generate program-relevant information to improve the ART treatment scale-up in South Africa.