Obesity constitutes one of the most serious public health problems, with rapidly increasing prevalence in western societies. Consequently, metabolic syndrome, a condition strongly associated with obesity, has become an epidemic problem. Recent studies have implicated chronic alterations to the stress system as playing a major role in the metabolic syndrome's pathophysiology. This brief review discusses the role of stress and hypothalamic-pituitary-adrenal axis dysfunction in the development of metabolic syndrome as well as new insights into the crosstalk between adipose tissue and endocrine stress system.