Iran has been one of the active countries fighting against HIV/AIDS in the Middle East during the last decades. Moreover, there is a strong push to strengthen the national health management system concerning HIV prevention and control. In Iran, HIV disease has its unique features, from changes in modes of transmission to improvement in treatment and care programs, which can make it a good case for closer scrutiny. The present review describes the HIV epidemic in Iran from the first case diagnosed until prevention among different groups at risk and co-infections. Not only we addressed the key populations and community-based attempts to overcome HIV-related issues in clinics, but we also elaborated on the efforts and trends in society and the actual behaviors related to HIV/AIDS. Being located in the Middle East and North Africa (MENA) region, given the countryspecific characteristics, and despite all the national efforts along with other countries in this region, Iran still needs to take extra measures to reduce HIV transmission, especially in health education. Although Iran is one of the pioneers in implementing applicable and appropriate policies in the MENA region, including harm reduction services to reduce HIV incidence, people with substance use disorder continue to be the majority of those living with HIV in the country. Similar to other countries in this region, the HIV prevention and control programs aim at 90-90-90 targets to eliminate HIV infection and reduce the transmission, especially the mother-to-child transmission and among other key populations.