Adipose tissue is an ‘endocrine organ’ that influences diverse physiological and pathological processes via adipokines secretion. Strong evidences suggest that epicardial and perivascular adipose tissue can directly regulate heart and vessels’ structure and function. Indeed, in obesity there is a shift toward the secretion of adipokines that promote a pro-inflammatory status and contribute to obesity cardiomyopathy. The prospect of modulating adipokines and/or their receptors represents an attractive perspective to the treatment of cardiovascular diseases. In this paper, we described the most important actions of certain adipokines and their receptors that are capable of influencing cardiovascular physiology as well as their possible use as therapeutic targets.