This Special Issue of AIDS Research and Human Retroviruses features results from the HIV Cure Initiative, funded by the California HIV/AIDS Research Program (CHRP). As a publicly funded grant maker, CHRP has served for more than three decades as a unique resource for innovative researchers in California, whose work seeks to address all aspects of the HIV epidemic and the communities affected by it. Early initiatives at CHRP pioneered what would become enduring cornerstones of HIV science: isolation of the virus; efficacy and toxicities of the first HIV treatments; the emergence of drug resistance; the first biospecimen banks for HIV-related research; the first community-based laboratory service for HIV diagnostic serology; and the first longitudinal case-control study of progression from HIV to AIDS-The San Francisco General Hospital Cohort. More recently, CHRP-funded conceptual studies of zinc-finger nuclease-mediated disruption of CCR5 genomic sequences and the safety of solid organ transplantation for HIV-positive patients have progressed from brilliant ideas to clinical realities, and CHRP is currently funding the first multisite trial of HIV preexposure prophylaxis for transgender persons in the United States. The present article outlines the founding of CHRP, our current grantmaking process, and our impact on HIV research over time. In 2013, CHRP launched a new initiative aimed at moving the then nascent frontier of HIV cure science forward: the CHRP HIV Cure Initiative provided over $1.4 million to multiple basic biomedical research projects, and selected results are presented in this Special Issue.