Appetite suppressant-related pulmonary hypertension and valvular heart disease are established disorders. Currently, the mechanism of these disorders is not certain. An estimated 6 million Americans and 70 million persons worldwide have been exposed to fenfluramine and dexfenfluramine. The clinical significance and long-term prognosis of cardiovascular effects and, thus, the potential public health effect of these disorders are not known. Longitudinal studies are required to further evaluate these disease processes. In addition, although isolated cases of regression of pulmonary hypertension and valve disease have been reported after the cessation of appetite suppressant therapy, the natural history remains uncertain.