To date, about 37 million people are living with the human immunodeficiency virus (HIV) and an estimated 680,000 people have died from acquired immune deficiency syndrome (AIDS) related illnesses globally. While all countries have been impacted by HIV, some have been significantly more impacted than others, particularly countries in sub-Saharan Africa. The purpose of this paper was to identify progress made in HIV prevention globally, particularly in the areas of voluntary counseling and testing (VCT) uptake, access to antiretroviral therapy (ART), and HIV-related stigma. With the development of ART, a cocktail of medications for the treatment of HIV, VCT uptake increased, as it became apparent that the medication would only be prescribed after an HIV diagnosis through testing. Widely considered a critical gateway to HIV prevention and treatment, VCT is being implemented in many countries, and as a result, about 38 million people living with HIV in 2018 had access to ART. Regardless of this success, major challenges still remain. We did an electronic search of 135 articles in English related to global HIV progress and challenges indexed in PubMed, ResearchGate, Google, and other search engines from 1998 to 2021. Sixty articles met the inclusion criteria for this paper. Data on trends in ART coverage were obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS) website. These data were used to show ART coverage globally in World Health Organization (WHO) regions. It was found that while global successes have been chalked in the areas of VCT uptake and ART coverage, HIV-related stigma has impeded greater success. This paper summarizes and discusses global successes and challenges in HIV prevention efforts in the past four decades with a focus on VCT, ART, and HIV-related stigma.