Objective. The objective of this paper is to describe HIV prevention programs conducted by nongovernmental organizations (NGO) that are meeting this challenge. Methods. One NGO undertaking HIV prevention programs was evaluated in each of the 23 countries participating in the Global AIDS Intervention Network (GAIN) Project throughout Latin America and the Caribbean. A two-stage selection process was used: (1) a search in databases and other information sources; (2) identification of NGOs that were best established and most actively engaged in HIV prevention activity. Executive directors were questioned about staffing, budget issues, populations served and barriers faced by these entities. Results. The 23 NGOs conducted 58 direct-service programs and had been conducting HIV prevention activities for a mean of 8 years (SD = 4.45; range 1-18 years). Average annual program budget was US$ 205 393 (range: US$ 10 000 to US$ 1 440 000). The NGOs reported a mean of 4.5 full-time employees (range 0-15, SD = 4.7). Many relied on volunteers (median = 10, mean = 51, range 0-700, SD = 150) to conduct HIV prevention activities. The NGOs provided prevention services for the general community (82.6%), children and adolescents (34.8%) and men who have sex with men (30.4%). Activities conducted by NGOs included train-the-trainer activities (43.5%) and face-to-face prevention activities (34.8%). Obstacles cited included lack of funding (60.9%) and HIV-related stigma and discrimination (56.5%). Conclusion. The strategies used by NGOs to overcome barriers to prevention are a testament to their ingenuity and commitment, and serve as examples for NGOs in other world regions.