Source control refers to the spectrum of physical measures that are undertaken to control a focus of infection, and to facilitate restoration of optimal anatomy and physiology. These measures are classified as drainage—the evacuation of infected liquid through the creation of a controlled sinus or fistula, debridement—the physical removal of necrotic infected tissue, device removal, and the definitive measures that comprise the process of reconstruction and rehabilitation. Effective and timely source control is critical to the successful management of life-threatening infection. This article reviews the principles of diagnosis and source-control management, and their application to common infections that result in severe sepsis and septic shock.