Acute infections in the face and neck can range from minor illnesses to life-threatening surgical emergencies with substantial morbidity and mortality. The cervicofacial soft tissues are compartmentalized in closely approximated spaces such that, despite fascial barriers, there is a high risk for trans-spatial spread with potentially dire consequences. Management relies heavily on understanding not only the anatomic detail but also on the etiopathogenesis and host factors. Delayed or inappropriate management can lead to potentially life-threatening complications. Moreover, the infection can have overlapping features with both neoplasm and chronic inflammation in the face and neck. Thus, systematic analysis of structures in the face/neck is critical for accurate and timely diagnosis. Focused attention on three specific elements—anatomic location of the abnormality (source), the region or compartment in which the abnormality dwells (space), and extent of the abnormality (spread)—can aid in the timely diagnosis, detection of complications, and guidance to appropriate management. In this chapter, we present a systematic approach to analyzing commonly encountered face and neck infections with emphasis on the complex interactions between source, space, and pathways of spread.