Musculoskeletal infection is commonly encountered in the emergency department and can take many forms, depending on the involvement of the various soft-tissue layers, bones, and joints. Infection may manifest as superficial cellulitis, necrotizing or nonnecrotizing fasciitis, myositis, a soft-tissue abscess, osteomyelitis, or septic arthritis. Because clinical parameters for the detection of musculoskeletal infection generally lack sensitivity and specificity, computed tomography (CT) plays an important role in the assessment of potential musculoskeletal infections in the emergency department. CT provides an analysis of compartmental anatomy, thereby helping to distinguish among the various types of musculoskeletal infection and to guide treatment options. Specific imaging features exist that help identify the numerous forms of infection in the bones and soft tissues, and CT is invaluable for detecting deep complications of cellulitis and pinpointing the anatomic compartment that is involved by an infection. Although all patients with musculoskeletal infection will require treatment with antibiotics, CT helps guide therapy toward emergency surgical débridement in cases of necrotizing fasciitis and toward percutaneous drainage in cases of abscess formation.