Infections of the appendicular musculoskeletal system may be caused by a broad range of pathogens involving its different components, such as bones, joints, and various soft tissues. The clinical presentations and imaging appearances of appendicular musculoskeletal infections vary considerably, dependent on factors such as the characteristics and virulence of the infecting organism, site of involvement, host factors, and duration of infection. These infections may be classified according to anatomical location, i.e., bones, joints, and soft tissues, with trauma and orthopedic hardware implantation being important risk factors. Further subclassification may be according to pathogens causing pyogenic, granulomatous, fungal, and parasitic infections. Achieving a prompt and accurate diagnosis helps facilitate appropriate treatment, prevent development of complications, and optimize clinical management and patient outcomes.