Burnout occurs in the context of an occupational hazard, specifically when workers become overwhelmed and exhausted by improperly managed chronic work stress. Although not a formal diagnostic entity, it is an officially recognized syndrome by the World Health Organization. Burnout may negatively impact quality of life, interpersonal relationships, and work performance and is associated with depression, sleep disturbance, and increased cardiovascular mortality. The contributing factors and management strategies of burnout will be reviewed in terms of psychological, biological, occupational perspectives and based on the epidemiologic triangle framework. The common phenomenologic and biological features of burnout suggest that it may share etiologic mechanisms with depression or trauma- and stress-related disorders. The assessment tools and differential diagnostic points of burnout compared to those of depression will also be discussed. A holistic approach that considers individual, work stress, and the occupational environment simultaneously is required to better manage and prevent burnout.