Musculoskeletal infections can affect the bones, joints, as well as soft tissues. Pathogens enter the target tissue by hematogenous spread, direct spread, or via direct entry through the damaged skin. The most common causative agents are bacteria that inhabit the skin. Infections can be classified according to location, pathogen, tissue involvement, mechanism of infection, duration or some other criterion. Bone and joint infections are often complex, represent a major cost to the healthcare system and may have potentially dangerous complications. Therefore, management of such infections requires an interdisciplinary approach and timely diagnosis to preserve the patient’s quality of life. In order to diagnose, it is necessary to take into account the clinical signs and symptoms, biochemical, microbiological and imaging methods. The first imaging method of choice is radiography, which depicts changes in the bones in two dimensions and is therefore not adequate in diagnosing early infection. The choice of further imaging depends on the type of infection and appropriate clinical suspicion. Computed tomography provides a detailed view of changes in the bones, while magnetic resonance imaging is the method of choice for evaluation of soft tissues and early signs of infection. Ultrasound is a valuable tool for diagnosing skin and superficial soft tissue infections, while nuclear medicine imaging techniques depict metabolic activity or the degree of inflammation in the tissue. The choice of antibiotics depends on the location and causative agents. In addition to antibiotics, osteomyelitis and prosthetic joint infection often require surgical treatment.