While investing in adolescents can foster growth and development opportunities, gender inequity and inadequate policy responses continue to undermine adolescent girls’ potential. The secondary effects of the COVID-19 pandemic exacerbate the health and development risks girls face. This article describes how the number of programs, policies, and studies targeting adolescent girls have increased in recent years, making higher quality evidence more available. However, systematic reviews of the evidence on intervention effectiveness often conclude with mixed results and implications. More research is needed on the under-explored dimensions of gender policies so policymakers can direct limited resources toward approaches proven to improve adolescent girls’ health, education, and wellbeing. Furthermore, ensuring the connection between evidence generation and evidence use remains an important—albeit unfinished—agenda, as demonstrated by case studies on evidence-informed policymaking for rural indigenous girls in Guatemala and girls at high risk of child marriage in Bangladesh. If adolescent girls are to thrive in tomorrow’s world, smarter investments are needed today to enable them to reach their full potential.