The presentation of different types of inflammatory arthritis, caused by autoimmunity, immune complexes, crystals, or cartilage damage, is clinically similar to native septic arthritis. The large microbiological spectrum of joint infection is one of the particularities distinguishing arthritis from other orthopedic infections such as osteomyelitis or implant-related infections. The current ... [Show full abstract] literature often defines orthopedic infections as “osteoarticular,” suggesting that diagnosis and treatment of bone and joint infection would be similar. Septic arthritis, osteomyelitis, and orthopedic implant–associated infections are different in nature, epidemiology, therapy, and outcome. This chapter underlines the particularities of native joint arthritis with an emphasis on diagnosis, epidemiology, treatment, and some prevention aspects before planned joint interventions. Most cases of primary septic arthritis and surgical site infections (SSIs) are due to Gram-positive pathogens, mainly Staphylococcus aureus. Posttraumatic cases show a greater variability with a higher proportion of Gram-negative and atypical pathogens.