Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of childhood and adolescence characterized by episodic bone pain. Diagnosis relies heavily on whole-body MRI and is made by excluding a wide variety of other disorders with overlapping imaging features, depending on location, marrow distribution, and the presence or absence of multifocality. We present an overview of the clinical and imaging features of CRMO and, through various clinical scenarios, provide tips for tailoring the differential diagnosis based on location and distribution of encountered abnormalities. Level of Evidence: 4 Technical Efficacy Stage: 3