The primary purpose of the right ventricle and pulmonary circulation is gas exchange. Because gas exchange occurs in thin, highly permeable alveolar membranes, pulmonary pressure must remain low to avoid pulmonary edema; because the right ventricle and the lungs are in series with the left ventricle and the systemic circulation, the entire cardiac output must pass through the lungs. This low pressure, high volume system, makes dramatically different demands on the right ventricle compared with the demands made on the left ventricle by the systemic circulation. Moreover, the right ventricle and pulmonary circulation must buffer dynamic changes in blood volume and flow resulting from respiration, positional changes, and changes in left ventricular cardiac output. The optimizations needed to meet these conflicting demands result in reduced capacity to compensate for increased afterload or pressure. Unfortunately, a large number of pathologic processes can result in acute and or chronic increases in afterload stress. As afterload stress rises, right heart failure may develop, and hemodynamic instability and death can occur abruptly. Several biochemical pathways have been identified that may participate in adaptation or maladaptation to excessive pressure loads.