Research policy observers are increasingly concerned about the potential impact of current academic working conditions on mental health, particularly in PhD students. The aim of the current study is threefold. First, we assess the prevalence of mental health problems in a representative sample of PhD students in Flanders, Belgium (N = 3659). Second, we compare PhD students to three other samples: (1) highly educated in the general population (N = 769); (2) highly educated employees (N = 592); and (3) higher education students (N = 333). Third, we assess those organizational factors relating to the role of PhD students that predict mental health status. Results based on 12 mental health symptoms (GHQ-12) showed that 32% of PhD students are at risk of having or developing a common psychiatric disorder, especially depression. This estimate was significantly higher than those obtained in the comparison groups. Organizational policies were significantly associated with the prevalence of mental health problems. Especially work-family interface, job demands and job control, the supervisor’s leadership style, team decision-making culture, and perception of a career outside academia are linked to mental health problems.