This paper offers guidance for novice nurse researchers on the ethical and methodological challenges of conducting health research in high school settings. Over the course of two studies in UK high schools with students aged 11–16 years, the authors encountered common ethical and methodological challenges. This article draws on these studies to build a critique of approaches to health research in school settings. Issues of consent and assent, confidentiality and participation can highlight tensions between the expectations of schools and health researchers. In this context, feasible research designs raise complex ethical and methodological questions. Ethical and methodological norms for health research may not be suitable for high school settings. Successful school-based health research designs may need to be flexible and responsive to the social environment of schools.