Musculoskeletal infections are diagnostic challenge because they are difficult to recognize in the early stages of the disease. Patients` initial evaluation includes history and physical examination, laboratory studies and radiological examinations. Earlier diagnosis and treatment help to reduce complications. The most common pathogen is Staphylococcus aureus. Other than gram negative and positive microorganisms, tuberculous or nontuberculous mycobacterial infections, brucellosis, typhus and syphilis, coccidioidomycosis, blastomycosis, histoplasmosis may be encountered. Due to the improvements in diagnosis methods, these infections have gradually been increasing. In the clinical prognosis of the patient, pathogen, patient characteristics, and infection source all play an important role. Age, immunosuppression, accompanying diseases (diabetes, rheumatoid arthritis, hypoxia etc.), presence of implant and foreign material, the blood supply and nutrition of the infected tissue may be counted as patient characteristics. Plain radiographs generally lack sensitivity and specificity at an early stage and usually not diagnostic. Computed tomography offers detailed bone anatomy however, lacks ideal sensitivity and specificity. Magnetic resonance imaging is considered the most sensitive modality, provides large anatomic detail, does not use ionizing radiation and has become the advanced imaging modality of choice in bone and soft tissue infections. Radionuclide modalities are also give valuable information for diagnosis. The source of the infection could be penetrative trauma, open fractures, animal or human bites or by means of inhalation, hematogenous dissemination and surgical contamination. These factors must be considered in determining the convenient treatment and the prognosis. In this chapter, clinical and radiological findings of infections of musculoskeletal system are going to be mentioned.