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As HIV incidence rises globally, Asian and Pacific Islander communities are increasingly affected. While often overlooked, Asian and Pacific Islander American women have shown the greatest percentage increase in HIV diagnosis rates. The development of a multilevel and multistrategy approach to HIV/AIDS education, prevention, and treatment among Asian and Pacific Islander females requires health care providers to identify personal and cultural barriers to prevention and treatment and implement culturally sensitive and specific measures. The purpose of this article is to illuminate barriers to HIV-related prevention, treatment, and care among Asian and Pacific Islander American females and provide practical application-based suggestions for providers, which may enhance Asian and Pacific Islander female inclusion in comprehensive HIV prevention.