Pulmonary Arterial Hypertension (PAH) is characterized by an increase in mean pulmonary arterial pressure due to an increase in pulmonary vascular resistance as a result of extensive vascular remodeling and vasoconstriction. In patients with PAH, the principal lesions involve intermediate and large-sized pulmonary arteries with medial and adventitial hypertrophy/hyperplasia in addition to lumen occluding plexiform lesions. A variety of cellular abnormalities have been described in the pulmonary vasculature that may play an important role in the development and progression of PAH, such as pulmonary endothelial dysfunction with altered synthesis of nitric oxide, thromboxane A2, prostacyclin and endothelin. Our understanding of the mechanisms of the disease further include the identification of mutations in cases of PAH and of potential stimuli of endothelial dysfunction like shear stress, autoimmunity, inflammation, drugs and viruses. Today three major categories of drugs for PAH are available: prostanoids, endothelin receptor antagonists and phosphodiesterase inhibitors. Therapy also may include anticoagulation, oxygen and calcium channel blockers. Treatment of pulmonary hypertension due to left heart diseases should be focused on the underlying cause. Further research and understanding of the pathophysiologic mechanisms of PAH should lead to further improvements in the treatment of this challenging disease.