Pulmonary hypertension (PH) is a debilitating disease with a poor prognosis. 
Therapeutic options remain limited despite the introduction of prostacyclin 
analogues, endothelin receptor antagonists and phosphodiesterase 5 inhibitors 
within the last 15 years; these interventions address predominantly the 
endothelial and vascular dysfunctionS associated with the condition, but simply 
delay progression of the disease rather than offer a cure. In an attempt to 
improve efficacy, emerging approaches have focused on targeting the 
pro-proliferative phenotype that underpins the pulmonary vascular remodelling in 
the lung and contributes to the impaired circulation and right heart failure. 
Many novel targets have been investigated and validated in animal models of PH, 
including modulation of guanylate cyclases, phosphodiesterases, tyrosine 
kinases, Rho kinase, bone morphogenetic proteins signalling, 5-HT, peroxisome 
proliferator activator receptors and ion channels. In addition, there is hope 
that combinations of such treatments, harnessing and optimizing vasodilator and 
anti-proliferative properties, will provide a further, possibly synergistic, 
increase in efficacy; therapies directed at the right heart may also offer an 
additional benefit. This overview highlights current therapeutic options, 
promising new therapies, and provides the rationale for a combination approach 
to treat the disease.