Animal models of pulmonary hypertension are used to evaluate new therapies, both their efficacy and the mechanism of their effect. They are also used to explore the biochemical mechanisms at work, with a view to identifying new drug targets. The limiting factor in each case is the extent to which the animal model represents the human condition; in particular, replicates the striking vascular pathology seen in lungs from patients with pulmonary hypertension. A telling observation is that therapies that have had dramatic effects in the animal models used to date have been far less impressive in clinical practice. New animal models have been described with marked intimal vascular lesions. In addition, genetically manipulated mice offer a targeted approach to examining signalling pathways. Comparisons of these models with the human pathology using unbiased genomic, proteomic and metabolomic platforms may reveal common pathogenic pathways and/or identify molecular signatures for personalized medicines. Animal models continue to have a role in the development of drugs for pulmonary hypertension but a clear understanding of their strengths and weaknesses is essential to the intelligent interpretation of data from their use.