The lesbian, gay, bisexual, and transgender (LGBT) population has been, and remains, disenfranchised in many ways. Despite increasing acceptance of sexual orientation, evidenced by recent strides in legalizing gay marriage in several states, LGBT people continue to have a higher prevalence of mental illness due to minority stress than heterosexuals. Factors such as stigma, prejudice, and discrimination lead to increased incidence of mental suffering as a result of stressful, hostile, and often unsafe environments. Prejudice within the LGBT community around race, gender, disability, or mental illness also exists. Transgender individuals have a high risk of being targeted for violence and hate crimes, harassment and discrimination, unemployment and underemployment, poverty, homelessness, substance abuse, suicide, and self-harm. The stressors that LGBT individuals face likely contribute to their disproportionate risk of contact with the criminal justice system beginning in adolescence and extending into adulthood. Transgender individuals in particular have a risk for incarceration, for reasons ranging from imprisonment based on gender identity expression alone to the need to earn money through the underground economy due to difficulty finding employment. In addition to homophobia and transphobia, LGBT individuals with mental illness experience further stigmatization. Clinicians need to understand the multiple stigmas that may affect an individual’s willingness to seek mental health care. The unique needs of incarcerated LGBT individuals with mental illness are often invisible, and generally misunderstood and underserved. This chapter seeks to add to the clinical knowledge of practitioners working with this population, to clarify legal precedent, and to establish best practices.