Despite major advances in understanding the mechanisms of disease and development of specific drug therapy, pulmonary arterial hypertension (PAH) remains a progressive, fatal disease. At present there are 3 classes of drug therapy for PAH: prostaglandins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. To maximize therapeutic benefit, and according to national and international guidelines, many patients are treated with combinations of these medications. This review presents a detailed account of the published data on the use of combination therapy in PAH. There are few randomized, placebo-controlled trial data to strongly support efficacy of most combination therapy, particularly oral combination therapy.