The diagnosis of venous thromboembolism (VTE) (deep vein thrombosis and pulmonary embolism) poses a challenge for physicians in emergency departments (EDs). Clinical findings and non-specific laboratory tests are usually insufficient to rule out VTE. Due to high costs, higher complication rates, and other reasons, the "gold standard" tests for VTE (pulmonary angiography or contrast venography) are usually unavailable and are seldom used by most physicians in the EDs. The end result is an extensive use of the non-invasive Imaging modalities and yet under-diagnosis of VTE. The purpose of this review is to describe the advanced non-invasive methods currently available for the diagnosis of VTE and to define the role of the rapid d-dimer assay. We also propose a practical diagnostic protocol for VTE that is based on a combination of D-dimer test and judicious use of non-invasive imaging, which may be implemented in all emergency departments.