Many studies have investigated the association between long working hours and health. By focusing on differences in the definition of long working hours and the influence of shift work, we attempt to explain why the results of these studies remain inconclusive. We defined long working hours as working time greater than around 40 hours per week or 8 hours per day. Since previous studies have indicated that shift work is detrimental to health, we minimized the influence of shift work in the studies. We also placed importance on the existence of reference groups since this made the results clearer. Based on these points, we analyzed previous studies to clarify the epidemiological evidence regarding the association between long working hours and health. We established inclusion criteria and carried out a systematic search for articles published in the Medline and PsycINFO databases between 1995-2012. We identified a total of 17 articles and 19 studies (12 prospective cohort and 7 cross-sectional studies). The outcomes were all-cause mortality, circulatory disease, diabetes mellitus, metabolic syndrome, depressive state, anxiety, other psychological disorders, sleep condition, cognitive function, and health-related behavior. Long working hours had significant adverse effects on most health outcomes. We concluded that working long hours is associated with depressive state, anxiety, sleep condition, and coronary heart disease. However, further studies that appropriately deal with the definition of long working hours and shift work are needed.