Septic arthritis and osteomyelitis are two of the most common diseases that affect bone and joints. Septic arthritis is a true rheumatologic emergency, mandating immediate joint drainage and antibiotics. Adult osteomyelitis most commonly arises from open fractures, diabetic foot infections, or surgical treatment of closed injuries. This chapter provides an overview of the etiology, diagnosis, and antimicrobial management of septic arthritis and adult osteomyelitis. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.