The activation of stress-related neuroendocrine systems helps to maintain homeostasis, but excessive stress can damage body functions. We review current evidence from basic sciences and epidemiology linking stress to the development and progression of metabolic disorders throughout life. Findings from rodents demonstrate that stress can affect features of metabolic dysfunction, such as insulin resistance, glucose and lipid homeostasis, as well as ageing processes such as cellular senescence and telomere length shortening. In human studies, stressors in the home, workplace and neighbourhood are associated with accelerated ageing and metabolic and immune alterations, both directly and indirectly via behavioural risks. The likelihood of developing clinical conditions, such as diabetes mellitus and hepatic steatosis is increased in individuals with adverse childhood experiences or long-term (years) or severe stress at work or in private life. The increased risk of metabolic disorders is often associated with other stress-related conditions, such as mental health disorders, cardiovascular disease and increased susceptibility to infections. Equally, stress can worsen prognosis in metabolic diseases. As favourable modifications in stressors are associated with reductions in incidence of metabolic disorders, further investigation of the therapeutic value of targeting stress in personalized medicine is warranted.