Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by nonresolving major-vessel pulmonary thrombi, believed to result from single or recurrent pulmonary thromboemboli. Because CTEPH is associated with high morbidity and mortality the recognition of patients who are at risk has become an important goal. While current data suggest that CTEPH does not result from traditional known thrombophilia or defective plasma fibrinolysis, it has been suggested that levels of Factor VIII and antiphospholipid antibodies (alongside increased lupus anticoagulant), two thrombophilic factors associated with recurrent thrombosis, are elevated in association with CTEPH. Additional risk factors have been evaluated in CTEPH patients including blood groups and lipoprotein (a). Certain medical conditions (splenectomy, ventriculo-atrial shunt/(infected) intravenous lines, acute PE and chronic inflammatory states) have been established as independent risk factors for CTEPH. In particular, the link between splenectomy and CTEPH has gained considerable attention, with speculation that abnormal post-splenectomy erythrocyte activities or abnormal platelet activation may be involved. Although some patients may be genetically susceptible to pulmonary arterial hypertension, genetic variants linked with CTEPH have yet to be determined. Improved understanding of risk factors for CTEPH is an important goal, allowing better targeting of at-risk groups, facilitation of appropriate intervention and potential limitation of disease progression.