The clinical diagnosis of acute pulmonary embolism (PE) is frequently considered in patients presenting to the emergency department or when hospitalized. Since symptoms are a-specific and the consequences of anticoagulant treatment are considerable, objective tests to either establish or refute the diagnosis have become a standard of care. Computed tomographic pulmonary angiography (CTPA), which has replaced pulmonary angiography as first-line imaging test, is associated with radiation exposure, several complications resulting from contrast dye administration, and over diagnosis. Importantly, CTPA can be avoided in 20% to 30% of patients who present with a first or recurrent episode of clinically suspected acute PE by using a standardized algorithm. This algorithm should always include a clinical decision rule to assess the likelihood that PE is present, followed by a D-dimer blood test and/or CTPA. The aim of this review is to provide clinicians this practical diagnostic management approach using evidence from the literature.