The pediatric patient with fever and knee effusion is always a cause for clinical concern. A thorough history and physical examination is required to guide appropriate diagnostic evaluation and management. Although pediatric knee effusions are common in the setting of trauma, the presence of fever should prompt consideration of infectious, rheumatologic, vasculitic, and malignant etiologies. This review covers the key components of the history, physical examination, diagnostic strategies, common etiologies, and initial management of the pediatric patient with fever and knee effusion.