Abstract Deep vein thrombosis (DVT) affects up to 2 million people in the United States, and worldwide incidence is 70 to 113 cases per 100,000 per year. Mortality from DVT is often due to subsequent pulmonary embolism (PE). Precise diagnosis and treatment is thereby essential for the management of DVT. DVT is diagnosed by a thorough history and physical examination followed by laboratory and diagnostic tests. The choice of laboratory and diagnostic test is dependent on clinical pretest probability. Available laboratory and diagnostic techniques mainly involve D-dimer test, ultrasound, venography, and magnetic resonance imaging. The latter two diagnostic tools require high doses of contrast agents including either radioactive or toxic materials. The available treatment options include lifestyle modifications, mechanical compression, anticoagulant therapy, inferior vena cava filter, and thrombolysis/thrombolectomy. All of these medical and surgical treatments have serious side effects including improper clot clearance and increased risk of hemorrhage occurrence. Therefore, research in this field has recently focused on the development of non-invasive and accurate diagnostics, such as ultrasound enhanced techniques and molecular imaging methods, to assess thrombus location and its treatment course. The frontier of nanomedicine also shows high prospects in tackling DVT with efficient targeted drug delivery. This review describes the pathology of DVT along with successive medical problems such as PE and features a detailed listing of various diagnostic and therapeutic modalities that have been in use and are under development.