question: INTRODUCTION Allostatic load refers to the cumulative burden of chronic stress and life events. It involves the interaction of different physiological systems at varying degrees of activity. When environmental challenges exceed the individual ability to cope, then allostatic overload ensues. Allostatic load is identified by the use of biomarkers and clinical criteria. OBJECTIVE To summarize the current knowledge on allostatic load and overload and its clinical implications based on a systematic review of the literature. METHODS PubMed, PsycINFO, Web of Science, and the Cochrane Library were searched from inception to December 2019. A manual search of the literature was also performed, and reference lists of the retrieved articles were examined.We considered only studies in which allostatic load or overload were adequately described and assessed in either clinical or non-clinical adult populations. RESULTS A total of 267 original investigations were included. They encompassed general population studies, as well as clinical studies on consequences of allostatic load/overload on both physical and mental health across a variety of settings. CONCLUSIONS The findings indicate that allostatic load and overload are associated with poorer health outcomes. Assessment of allostatic load provides support to the understanding of psychosocial determinants of health and lifestyle medicine. An integrated approach that includes both biological markers and clinimetric criteria is recommended.