This issue of the Infectious Disease Clinics of North America contains a current overview of the relationship between infections and the musculoskeletal system. Infection affects a considerable segment of the population, constitutes a significant cause of morbidity and mortality, and adds to the cost of taking care of patients with musculoskeletal involvement. Unraveling the mystery of this important correlation aids clinical practitioners in the treatment and prevention of rheumatic diseases. Specific articles are devoted to PCR applications; soft-tissue infections; septic arthritis; imaging studies; reactive arthritis; infection in connective tissue diseases, hepatitis C; HIV; retrovirus; and the impact of biologic agents.