There are substantial gaps in knowledge about opioid misuse in girls and women after decades of underrepresentation of females in preclinical and clinical research. As the difference in opioid misuse prevalence between men and women narrows, the need to fill these knowledge gaps is becoming even more urgent. This commentary discusses a recent study by Bagley and colleagues which provides important and timely information about trends and sex differences in nonfatal opioid overdoses in adolescents and young adults, an age group with unique risk.