Chest pain is a challenging clinical problem in the emergency department. Despite advances in clinical diagnosis, many patients with atypical chest pain are needlessly hospitalized and others are mistakenly discharged. Faced with the specific clinical situation in which a patient has chest pain, an initially normal or inconclusive electrocardiogram, and normal cardiac biomarkers, multislice CT has proven useful for ruling out the conditions that involve the greatest morbidity and mortality and for establishing the cause of pain. This article reviews the current usefulness of multislice CT in the diagnostic workup of patients presenting at the emergency department with chest pain. We review the technique, define the most appropriate population, describe the acquisition protocols, and discuss the advantages and disadvantages of each study protocol.