Cross-sectional and longitudinal studies indicate a positive association between obesity and depression. While some evidence suggests that depression is a risk factor for obesity, other findings indicate that obesity is a risk factor for depression. Therefore the directionality of this relationship remains unclear. Alternatively, there may be common mediating biological or environmental contributors accounting for this association. Potential biological mediators include dysregulation of the HPA axis, leptin resistance, and inflammatory immune responses. Environmental and psychological mediators may include a history of abuse and binge eating. It is also possible that the association between obesity and depression is most pronounced among particular subsets of individuals (e.g., women, those with more severe obesity). A better understanding of this depression-obesity association is needed to guide treatment recommendations for obese clients with comorbid depression. Future research is also needed to determine who is most vulnerable to experiencing comorbid depression and obesity.