Bone and joint infections, including osteomyelitis, septic arthritis, prosthetic joint infections, and spinal infections, represent a significant challenge in clinical practice due to their complex pathophysiology, diagnostic difficulties, and potential for serious complications. This chapter provides a comprehensive overview of the mechanisms of infection spread—hematogenous, contiguous, and direct inoculation—and outlines the varied clinical presentations across different patient populations. Emphasis is placed on a multidisciplinary approach for diagnosis using imaging, microbiology, and molecular techniques such as sonication and PCR. Treatment strategies include long-term antibiotic therapy, surgical debridement, and the use of local antibiotic delivery systems. Emerging therapies, including hyperbaric oxygen therapy, calcium sulphate beads, genomic tools, and bacteriophages, are also discussed. Through illustrative case examples and recent advancements, the chapter underscores the importance of timely, collaborative, and individualized patient care.