Lesbian, gay, bisexual, and transgender (LGBT) youths comprise a diverse population with unique developmental experiences and needs. Many experience some form of anti-LGBT stigma. Although most LGBT youths cope well and are free from mental illness, they are at increased risk for a number of psychiatric and other health problems compared with the general population. These problems include depression, anxiety, suicidality, tobacco and substance use, and disordered eating. These disorders are significant sources of morbidity and mortality and are risk factors for other health problems, including HIV and other sexually transmitted infections. Preliminary evidence suggests the same is true for gender dysphoric youths. The minority stress hypothesis holds that exposure to LGBT-specific stigma causes these disparities among LGBT youth. During the past decade, increasing attention has been devoted to developing evidence-based practice guidelines to address the mental health needs of LGBT youths, with an emphasis on core clinical competencies for practitioners working with this population. This review addresses key principles for mental health promotion and care of LGBT youths. Key resources for clinicians and two clinical vignettes are included.