Objective: The HIV/AIDS burden in Israel is increasing. This study aims to describe the nationwide-HIV epidemiology in the last 30 years and highlight areas of concern in HIV/AIDS control. Design: Descriptive study. Setting: The National HIV/AIDS Registry in Israel. Participants: All individuals who were reported with HIV/AIDS in Israel. Primary outcome measures: Classification of HIV/AIDS cases by risk groups, calculation of annual trend analysis and estimation of HIV transmission rates by dividing the annual HIV/AIDS-incidence by the prevalence, while the number of newly diagnosed HIV/AIDS cases reported was a proxy of the incidence. Results: From 1981 to 2010, 6579 HIV/AIDS cases were reported in an upward trend from 3.6 new HIV diagnoses/100 000 population in 1986 to 5.6 in 2010. Immigrants from countries of generalised epidemic (ICGE) comprised 2717 (41.3%) of all cases: 2089 (76.9%) were Israeli citizens and 628 (23%) were non-Israeli citizens, mostly migrant workers. The majority (N=2040) of ICGE Israeli citizens were born in Ethiopia. Only 796 (12.1%) of all HIV/AIDS cases were heterosexuals who were non-ICGE and not injecting drug users (IDUs). IDU comprised 13.4% (N=882) of all cases. Men who have sex with men (MSM) accounted for 33.2% (N=1403) of all men reported, while the annual number of MSM reported with HIV/AIDS has quadrupled between 2000 and 2010. It is estimated that the HIV point prevalences in 2010 for Ethiopian-born Israeli citizens, IDU and MSM aged 16-45 were 1805, 1492 and 3150, respectively. The crude estimated transmission rates among Israeli citizens, excluding the Ethiopian-born, was 10.5, while among Ethiopian-born Israeli citizens, IDU and MSM the rates were 3.6, 6.3 and 13.2, respectively. Conclusions: The HIV/AIDS burden in Israel is low among heterosexuals and higher in risk-groups. Among these risk groups, the highest HIV transmission rate was in MSM, followed by IDU and ICGE. Culturally sensitive and focused prevention interventions should be tailored exclusively for each of the vulnerable risk groups.