Although pulmonary embolism (PE) is often considered a difficult diagnosis to establish, important clinical clues and properly ordered laboratory and imaging tests can reliably detect or exclude this potentially fatal condition. This article will provide a practical approach to recognizing clinical situations in which PE should be suspected. This guide to PE diagnosis will be tailored to those with busy practices, outlining a focused history and physical examination as well as optimal strategies for test ordering. Instead of performing an encyclopedic laundry list of tests, clinicians can pick and choose carefully among them, which maximizes efficiency and cost-effectiveness. The choice of tests is flexible, thus allowing the clinician to utilize the strengths of the particular hospital in which the patient is evaluated. This article will help ensure that patients with PE are identified rapidly and, conversely, that those without PE will undergo an appropriate workup for other important medical conditions. With a 3-stage approach consisting of (1) clinical evaluation; (2) nonimaging laboratory tests; and (3) imaging tests, PE can often be quickly detected with a definitive evaluation.