Obesity is fast becoming the scourge of our time. It is one of the biggest causes of death and disease in the industrialized world, and affects as many as 32% of adults and 17% of children in the USA, considered one of the world's fattest nations. It can also cost countries billions of dollars per annum in direct and indirect care, latest estimates putting the USA bill for obesity-related costs at $147 billion in 2008. It is becoming clear that the pathophysiology of obesity is vastly more complicated than the simple equation of energy in minus energy out. A combination of genetics, sex, perinatal environment and life-style factors can influence diet and energy metabolism. In this regard, psychological stress can have significant long-term impact upon the propensity to gain and maintain weight. In this review, we will discuss the ability of psychological stress and ultimately glucocorticoids (GCs) to alter appetite regulation and metabolism. We will specifically focus on (i) GC regulation of appetite and adiposity, (ii) the apparent sexual dimorphism in stress effects on obesity and (iii) the ability of early life stress to programme obesity in the long term.