This ethnographic qualitative study explored the needs of transgender people of color, including biological transitioning issues, gender and group membership identity formation, HIV, and other health issues. The sample consisted of transgender youth and adults of color in San Francisco (N = 43). Data were collected from in-depth interviews with 20 youth and adults and focus groups with 23 individuals. The study focused on perspectives of racial and ethnic minorities from Asian/Pacific Islander, African American, and Latino backgrounds. The medical decision-making perspective was used to gain a deeper understanding of sociocultural and psychological factors affecting transgender individuals of color in San Francisco. The major themes that emerged were gender identity, group membership, transitioning and related issues, sex work, alcohol and drug use, mental health and health care, sense of community, HIV, resources, and other support. Key clinical considerations that health providers can use to improve care of transgender individuals of color are included.