Graduate students are more than six times as likely to experience depression compared with the general population. However, few studies have examined how graduate school specifically affects depression. In this qualitative interview study of 50 life sciences PhD students from 28 institutions, we examined how research and teaching affect depression in PhD students and how depression in turn affects students' experiences teaching and researching. Using inductive coding, we identified factors that either positively or negatively affected student depression. Graduate students more commonly mentioned factors related to research that negatively affected their depression and factors related to teaching that positively affected their depression. We identified four overarching aspects of graduate school that influenced student depression: the amount of structure in teaching and research, positive and negative reinforcement, success and failure, and social support and isolation. Graduate students reported that depression had an exclusively negative effect on their research, primarily hindering their motivation and self-confidence, but that it helped them to be more compassionate teachers. This work pinpoints specific aspects of graduate school that PhD programs can target to improve mental health among life sciences graduate students.