Pulmonary embolism (PE) is an extremely common and highly lethal condition that is a leading cause of death in all age groups. Over the past 10 years, computed tomography (CT) scanners have gained acceptance as a minimally invasive method for diagnosing PE. In this book, a framework for computer-aided diagnosis of PE in contrast-enhanced CT images is presented. It consists of a combination of a method for segmenting the pulmonary arteries (PA), emboli detection methods as well as a scheme for evaluating their performances. The segmentation of the PA serves one of the clot detection methods, and is carried out through a region growing method that makes use of a priori knowledge of vessel topology. Two different approaches for clot detection are proposed: the first one performs clot detection by analyzing the concavities in the segmentation of the pulmonary arterial tree. It works in a semi-automatic way and it enables the detection of thrombi in the larger sections of the PA. The second method does not make use of PA segmentation and is thus fully automatic, enabling detection of clots farther in the vessels. The combination of these methods provides a robust detection technique that can be used as a safeguard by radiologists, or even as preliminary computer-aided diagnosis (CAD) tool. The evaluation of the method is also discussed, and a scheme for measuring its performance is proposed, including a practical approach to making reference detection data, or ground truths, by radiologists.