Mineralocorticoid receptor (MR) has been recently identified in adipose tissue, where its excessive activation contributes to several metabolic derangements often observed in obesity and metabolic syndrome. Recent findings support the existence of a bidirectional cross-talk between adipose tissue and adrenal glands, contributing to obesity-related hyperaldosteronism and subsequent adipocyte MR excessive activation. In this regard, MR pharmacological blockade has led to prevention of weight gain and metabolic benefits in murine models of genetic or diet-induced obesity. However, there is still a lack of knowledge on the potential metabolic effects of MR antagonists in clinical settings. Hence, larger clinical studies are deemed necessary to clarify the role of MR antagonism in obesity and metabolic syndrome in humans.