Venous thromboembolism (VTE) is a common disorder that can lead to substantial morbidity and mortality through the clinical manifestations of deep vein thrombosis (DVT) and pulmonary embolism (PE). Although rapid diagnosis and treatment are critical in preventing PE, mortality and major morbidity due to conditions such as postthrombotic syndrome may complicate the differential diagnosis of VTE. The clinical symptoms associated with DVT are neither sensitive nor specific and can be indicative of a wide range of diagnoses. Because imaging studies can be expensive and are sometimes inconclusive, they should be used judiciously in patients with highly suspected VTE. This review offers a clinical perspective on the accurate, routine diagnosis of VTE, including an overview of common clinical signs and symptoms, as well as the advantages and drawbacks of available diagnostic strategies.