HIV/AIDS is among the leading causes of morbidity and mortality in world. There are more than 35 million people living with HIV/AIDS in the world. Although the annual incidence of HIV infection is decreasing globally, HIV prevalence is rising due to development of more effective treatment and higher survival. Iran suffers from concentrated HIV epidemics among injecting and non-injecting drug users. There are more than 27 thousand registered cases of HIV infection and it is estimated that there are above seventy eight thousand cases in the country. Regarding the burden of disease, it is projected that HIV/AIDS will have the highest growth during the next 10 years. The outcome of this epidemics will be determined by human behavior. HIV, psychiatric disorders and substance use disorders are closely correlated and are accompanied by similar risk factors. They also share common consequences such as stigma and discrimination. Correlation of psychiatric disorders, as one of the most influential determinants of our behavior, and HIV/AIDS infection is reviewed in this narrative article. Psychiatric disorders are associated with greater risk of HIV acquisition. Substance use disorders, both injecting and non-injecting, as well as severe mental illnesses put the individual at higher risk of acquiring HIV infection. Impaired judgment, diminished inhibition and control over behaviors, lack of insight and poor self-care have been proposed as the underlying mechanisms. On the other hand, HIV infection may put the individual at greater risk of developing a mental illness. Coping with a chronic and lifethreatening illness, fear of stigma and discrimination, CNS invasion of the virus as well as the adverse neuropsychiatric side effects of anti-retroviral medications may all contribute to establishment of a psychiatric disorder. Although there exists a bi-directional correlation between mental health problems and HIV/AIDS infection, this reciprocity goes beyond. Psychiatric disorders can affect the patient’s adherence, access to treatment and care and can worsen the course and clinical outcome of the infection. The clinical importance, underlying mechanism and other implications of this correlation are reviewed in this article. © 2016, Tehran University of Medical Sciences. All rights reserved.