INTRODUCTION In the past few decades, mental health problems have increasingly contributed to sickness absence and long-term disability. However, little is known about prognostic factors of return to work (RTW) and disability of persons already on sick leave due to mental health problems. Understanding these factors may help to develop effective prevention and intervention strategies to shorten the duration of disability and facilitate RTW. METHOD We reviewed systematically current scientific evidence about prognostic factors for mental health related long term disability, RTW and symptom recovery. Searching PubMed, PsycINFO, Embase, Cinahl and Business Source Premier, we selected articles with a publication date from January 1990 to March 2009, describing longitudinal cohort studies with a follow-up period of at least 1 year. Participants were persons on sick leave or receiving disability benefit at baseline. We assessed the methodological quality of included studies using an established criteria list. Consistent findings in at least two high quality studies were defined as strong evidence and positive findings in one high quality study were defined as limited evidence. RESULTS Out of 796 studies, we included seven articles, all of high methodological quality describing a range of prognostic factors, according to the ICF-model categorized as health-related, personal and external factors. We found strong evidence that older age (>50 years) is associated with continuing disability and longer time to RTW. There is limited evidence for the association of other personal factors (gender, education, history of previous sickness absence, negative recovery expectation, socio-economic status), health related (stress-related and shoulder/back pain, depression/anxiety disorder) and external i.e., job-related factors (unemployment, quality and continuity of occupational care, supervisor behavior) with disability and RTW. We found limited evidence for the association of personal/external factors (education, sole breadwinner, partial/full RTW, changing work tasks) with symptom recovery. CONCLUSION This systematic review identifies a number of prognostic factors, some more or less consistent with findings in related literature (mental health factors, age, history of previous sickness absence, negative recovery expectation, socio-economic status, unemployment, quality and continuity of occupational care), while other prognostic factors (gender, level of education, sole breadwinner, supervisor support) conflict with existing evidence. There is still great need for research on modifiable prognostic factors of continuing disability and RTW among benefit claimants with mental health problems. Recommendations are made as to directions and methodological quality of further research, i.e., prognostic cohort studies.