Youth who are lesbian, gay, bisexual, queer, and questioning (LGBQ PLUS_SPI ) and youth who are a gender distinct from their birth-assigned sex (i.e., transgender and gender diverse), collectively LGBTQIA PLUS_SPI , show nearly triple the risk for self-injurious thoughts and behaviors (SITBs). Research to date highlights that minority stressors across structural, interpersonal, and intrapersonal levels may help to explain this heightened risk. This chapter reviews the research linking stress across each of these levels on LGBTQIA PLUS_SPI SITBs. Moreover, this chapter reviews evidence-based treatments to reduce SITBs in LGBTQIA PLUS_SPI youth, highlighting that interventions that reduce minority stressors and increase coping skills in the context of minority stress appear most effective. In addition to inter- and intrapersonal-level interventions, we argue that major structural changes are needed to meaningfully reduce elevated risk for SITBs in LGBTQIA PLUS_SPI youth.