Resistin, a 12.5-kDa polypeptide, has been associated with both insulin resistance and inflammation in animal models. Although initially discovered in the adipocytes, it has subsequently been found in other tissues. In humans, controversy still exists regarding the role of resistin but serum resistin concentration has been correlated with risk factors for coronary heart disease, renal dysfunction and outcomes among stroke patients. Both inflammation and insulin resistance are associated with the development of incident heart failure, with worse outcomes among those with prevalent cardiomyopathy. Therefore, it is interesting to note that recent literature suggests a significant relationship between serum resistin concentrations and heart failure. In this article, we discuss the physiology, pathophysiology, and the direct and indirect role of resistin in determining heart failure risk and worse outcomes among these patients. Some of the salient points reviewed include the possible association of resistin with hyperglycemia and substrate metabolism, inflammation through TNF-alpha and direct cardiac effects.