Introduction: Maslach defined burnout syndrome first time as a syndrome involving (i) exhaustion, (ii) “depersonalization” – lack of empathy for or detachment from service recipients, and (iii) a reduced sense of professional accomplishment. Burnout leads to changes in autonomic system, immune and endocrine system. The aim of this paper was therefore to provide an overview of the literature on clinically significant burnout and their potential neurobiological and physiological correlates.Methods: All English articles published between till October 2021 were searched in PubMed, Science-Direct, Medline, GoogleScholar, using the keywords, burnout, hypothalamic-pituitary-adrenal-axis, cortisol, stress, neurobiology, neurogenesis, BDNF, immune, biological, sympathetic, parasympathetic, autonomic nervous system, endocrine, metabolic, cognition, sleep, and neuroimaging in various combinations. The full text of relevant articles was obtained and their reference lists were reviewed for additional studies.Results: Burnout leads to alteration in autonomic, endocrine and immune system marked by deranged levels of various hormones and immune markers. It is also reflected as neuroimaging changes in various brain structures and may manifest as cognitive changes. Accelerated aging, increased risk of cardiovascular diseases and type II diabetes mellitus, increased allosteric load are some other manifestations of burnout that needs clinical attention.Conclusion: Future research with more homogeneous clinical samples, prospective experimental designs and challenge tests will help to delineating the underlying biological mechanisms of burnout. This will help to point to potential treatment targets.