SAPHO and recurrent multifocal osteomyelitis are complex inflammatory conditions that clinical radiologists play an essential part in diagnosing. They present with a wide range of musculoskeletal and skin manifestations, and exhibit several key diagnostic features that, when present, make the diagnoses unequivocal. The overall population group is young. Diagnostic delay is common with a relapsing and remitting clinical course and often subtle early radiologic findings. This article provides an up-to-date insight into both conditions, including their multifaceted pathogenesis, effective therapeutic options, and advanced imaging features, to arm radiologists with the knowledge required to make the diagnoses confidently in a timely manner.