Venous thrombosis is a cause of considerable morbidity and mortality. Over the past several years, several new causes of thrombophilia have been identified and have dramatically altered the approach to patients presenting with thrombosis. Newly described abnormalities associated with thrombophilia include the syndrome of activated Protein C resistance (APCR), the prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of coagulation factors VIII and XI. Clinicians can now frequently determine causes of thromboses that have previously been deemed idiopathic. Though the risk factors for VTE are becoming better defined, the cost-effective approach to diagnosis and therapeutic implications are not entirely clear at this point.