Hereditary, or inherited, thrombophilias are associated with an increased risk of venous thrombosis (VTE) and, to a lesser degree, arterial thrombosis. However, testing for hereditary thrombophilia remains controversial. This is because the results of hereditary thrombophilia testing often are not sufficiently predictive to affect management and can cause harm. Many other factors impact management decisions, including age at diagnosis, family history of VTE, site of VTE, and presence of provoking factors like hospitalization, trauma, pregnancy, malignancy, immobility, or surgery. Nevertheless, a nuanced understanding of the pathophysiology of hereditary thrombophilias and how to integrate the information testing provides into clinical practice is key to providing evidence-based and patient-centered care. This chapter reviews the pathophysiology and best practices for hereditary thrombophilia testing drawn from existing data, international society guidelines, and consensus expert opinion. Of note, this chapter does not address acquired causes of thrombophilia, including antiphospholipid syndrome, myeloproliferative neoplasm, or paroxysmal hemoglobinuria, nor do we discuss arterial thrombosis. Instead, we focus on 3 key topics: (1) pathophysiology of hereditary thrombophilia, (2) nuances of ordering, interpretation, and clinical application of testing, and (3) indications for testing.