Pyomyositis is the primary infection of skeletal muscles, accompanied by abscess formation in the suppurative phase but may be without a focal fluid collection in the presuppurative phase. We describe three patients, one with insulin-dependent diabetes mellitus, another with sickle cell disease, and the third a previously healthy child with varicella infection who developed pyomyositis. Ultrasound or magnetic resonance imaging suggested the diagnosis in each case. The patients were treated with intravenous antibiotic therapy and two required abscess drainage. The infection in the third resolved without surgical drainage. None of our patients had residual functional limitations. We believe that a high index of suspicion and prompt diagnosis can prevent complications from pyomyositis.