Many guidelines suggest incorporating clinical assessment, imaging, and D-dimer testing into diagnostic algorithms in patients with suspected deep venous thrombosis (DVT) and pulmonary embolism (PE). This special article reviews the evidence supporting the use of algorithms and their individual components for diagnosis of upper- and lower-extremity DVT and PE in adults, including pregnant women. The authors identified evidence through several electronic database searches to April 2017, evaluated the robustness of selected evidence, assessed whether diagnostic approaches that do not use algorithms are acceptable, and identified knowledge gaps that require further research.