The challenge-hindrance stress framework argues that certain job stressors have entirely detrimental effects (hindrance stress), but some may also have beneficial effects (challenge stress). Though the challenge-hindrance framework has largely been neglected in teacher stress research, we adopted it to provide a more differentiated view of the most prominent stressors in the teaching profession. We asked a sample of 528 secondary schoolteachers to report the extent to which they perceived occupation-specific stressors as motivating (challenge stress) and burdening (hindrance stress). Most stressors (those associated with sociopolitical pressure, students' misbehavior, and lack of resources) were seen as a hindrance rather than a challenge. Only stressors associated with expanded job scope seem to have had more challenge than hindrance potential. Teachers' hindrance (but not challenge) stress in turn was a strong predictor of psychophysiological symptoms. Importantly, hindrance stress was highest and also the most significant predictor of psychophysiological symptoms if it arose from sociopolitical pressure. In sum, the results indicate that the challenge-hindrance framework might serve as a useful theoretical background in the field of teacher stress research and could offer another explanation for the poor health reported by this occupational group.