Considerable research documents that LGBTQ youth are more likely to experience mental health challenges than their heterosexual peers, including higher rates of depression and suicidal thoughts and behaviors. This first Science-to-Practice Brief summarizes a study on protective factors related to depression and suicidality among U.S. sexual and gender minority adolescents. It emphasizes the need for school professionals to consider the impact of the intersectionality of LGBTQ students' sexual orientation, gender identity, sex, and race/ ethnicity, and it summarizes specific recommendations for implementing multitiered systems of support for LGBTQ youth in schools.