Musculoskeletal infection encompasses a wide variety of tissues (joints, bone, tendons, discs, soft tissues) and manifestations depending on the infective organism and its degree of acuity. The varied appearances on imaging modalities represent a basic skill necessary for the practicing radiologist. Infection can have devastating consequences, and accurate and rapid diagnosis is paramount. Additionally, there are a number of noninfectious conditions that can simulate infection on imaging or clinically. This chapter will address imaging appearances of musculoskeletal infection and differential diagnosis including noninfectious mimics.