The clinical condition of patients with chronic pulmonary arterial hypertension (PHT) often deteriorates progressively, despite monotherapy with presently available groups of drugs: prostanoids, endothelin-receptor antagonists and phosphodiesterase-5-inhibitors. In such situations there is in principle the opportunity of giving a combination of drugs, especially as one can expect synergistic effects. Trials with a small number of patients have indicated that the combination of inhaled iloprost and bosentan, inhaled iloprost and sildenafil or bosentan and sildenafil are more efficacious than any one of these drugs taken as monotherapy. The decision when to use a combination treatment should be made on the basis of defined targets that are of significant prognostic value. It should be considered for patients in NYHA class III or IV, if monotherapy has not achieved the desired efficacy. Combination treatment with two or three of the mentioned drugs are being tested as part of controlled studies of their efficacy and safety: they currently constitute the most important therapeutic advances. Analogously to the management of heart failure, combination therapy is likely to be the standard treatment of PHT in future, with the aim of providing optimal results for exertional capacity and lasting functional stability.