This review describes recent advances in understanding the pathophsiologic basis of the hypercoagulable states and presents a framework for a systematic clinical approach to patients. Hypercoagulability is broadly defined as encompassing 2 clinical situations: 1) the presence of laboratory abnormalities or clinical conditions considered to be associated with an increased risk of thromboembolic complications (prethrombotic states) and 2) recurrent thrombosis in patients with no recognizable predisposing factors (thrombosis-prone patients). Primary hypercoagulable states are generally inherited abnormalities in which a physiologic anticoagulant mechanism is defective (eg antithrombin III deficiency). Secondary hypercoagulable states are generally acquired disorders in patients with underlying systemic diseases or clinical conditions such as pregnancy or use of oral contraceptives that are known to be linked to an increased risk of thrombosis. Laboratory testing should be directed at the diagnosis of a specific primary or secondary hypercoagulable state. Among the factors that may indicate a primary hypercoagulable state are a family history of thrombosis, recurrent thrombosis without apparent precipitating factors, thrombosis at unusual anatomic sites, thrombosis at an early age, and resistance to conventional antithrombotic therapy. Testing should also be directed at identifying any underlying systemic disorder since treatment may improve the thrombotic tendendy.