Many students participate in a wide range of school or community-based extracurricular programs. Although there is strong evidence such programs promote healthy development programs that specifically serve sexual and gender minority students (e.g., lesbian, gay, bisexual, transgender, or queer/questioning [LGBTQ] students), and that address pressing issues affecting these students, have received far less attention than other programs. Yet LGBTQ students face enduring concerns at school. Because of the potential for school-based extracurricular groups to shape school climate, address inequality, and affect student performance, there have been calls to identify programs and settings that may reduce discrimination against LGBTQ students, promote their well-being, and foster safe and affirming school environments. Gay-Straight Alliances (GSAs) show promise for accomplishing these goals. GSAs are school-based extracurricular groups that provide a setting for LGBTQ students and their peer allies to receive support, socialize with one another, learn about LGBTQ issues, and advocate for equity and justice in schools. As a result, GSAs aim not only to support their immediate members but also to improve the experiences of students within the whole school. As GSAs become increasingly present in middle and high schools across the United States, it is important to understand how they can be most effective. This article begins with an overview of GSAs and how they operate. Next, it reviews findings that show GSAs are tied to positive student outcomes, highlights some of the ways GSAs promote well-being, and offers suggestions for how they can benefit youth from many different backgrounds. It then describes the roles and experiences of GSA advisors, as well as how they can support GSA members. The article concludes by noting how GSAs can partner with other school-based efforts to promote the well-being of LGBTQ students and contribute to better social and academic experiences for all students.