Adolescents assume increased responsibility for their health, particularly regarding health decision-making for lifestyle behaviors. Prior research suggests a relationship between health literacy (HL) and health behaviors in adolescents. Yet, the specific role of HL in adolescents' health decision-making is unclear. This study qualitatively explored adolescents' use of HL in their health decision-making. Six focus groups with adolescents (N = 37, M = 16.49, 86% girls) were conducted. Adolescents' responses to questions about their HL use were coded using thematic analysis. Adolescents identified passive and active HL engagement and several individual (eg, future orientation, risk perception) and environmental (eg, access to resources/information, media) factors that influenced their use of HL in health decision-making. Feedback from others, subjective health, and ability to navigate multiple sources of information also determined adolescents' confidence in their HL skills. Our results support expanding the types of HL studied/measured in adolescents and provide insight on how HL can be leveraged to improve adolescents' health decision-making. Though there was no guiding theory for this study, results support using the Information-Motivation-Behavior Skills model to assess the HL/health decision-making relationship in adolescence.