Despite ample evidence that right ventricular function is a critical determinant of the clinical response to a spectrum of cardiovascular diseases, there has been only a limited analysis of the unique and distinguishing physiologic properties of the RV under normal circumstances and in response to pathologic insults. This knowledge deficit is increasingly acknowledged. This review highlights some of these features and underscores the fact that rational therapy in RV failure needs to acknowledge its unique physiology and ought to be chamber specific. That is proven therapies for LV dysfunction do not necessarily apply to the RV. The updated version of this review now acknowledges recent advances in the understanding of metabolic, inflammatory and gender-specific influences on the right ventricle.