Bone and joint infections include septic arthritis, prosthetic joint infections, osteomyelitis, spinal infections (discitis, vertebral osteomyelitis and epidural abscess) and diabetic foot osteomyelitis. All of these may present through the acute medical take. This article discusses the pathogenesis of infection and highlights the importance of taking a careful history and fully examining the patient. It also emphasises the importance of early surgical intervention in many cases. Consideration of alternative diagnoses, appropriate imaging and high-quality microbiological sampling is important to allow appropriate and targeted antimicrobial therapy. This article makes some suggestions as to empiric antibiotic choice; however, therapy should be guided by local antimicrobial policies and infection specialists. Involvement of a multidisciplinary team is essential for optimal outcomes.