Connective tissue diseases (CTD) are commonly complicated by pulmonary arterial hypertension (PAH) which is often the leading cause of death in this population. Despite recent advances in therapy for PAH in general, the response to treatment in patients with CTD, particularly patients with scleroderma-associated PAH (SSc-PAH), has been quite discouraging. This chapter reviews the pathophysiology, clinical manifestations, and current and promising therapy for CTD-associated PAH with a particular focus on SSc-PAH. The lack of clinical response to modern therapies may merely reflect the limitations of traditionally employed PAH outcome measures in CTD-associated PAH patients or highlight the heterogeneity of the disease manifestations within this group of patients. Importantly, since involvement of vital organs other than the lung, such as the gastrointestinal tract and the kidneys (particularly in SSc-PAH), may limit candidacy for lung transplantation, new therapies that target abnormal cellular proliferation in the pulmonary vasculature that are currently under investigation may be of particular relevance in this syndrome.