Knee pain is a common presenting complaint in the emergency department, and although the major etiologies are overuse and degenerative, inflammatory and infectious causes must be ruled out. This issue reviews the potential causes of knee pain from the history and physical examination, symptom location based differential, clinical clues, and special testing strategies. Evidence on the uses of x-ray and ultrasound for diagnostic imaging is reviewed. For suspected infectious causes, procedures for palpation-guided and ultrasound-guided arthrocentesis are outlined. Treatment strategies are summarized, with evidence on the effectiveness of weight loss, physical therapy, orthotics, medication therapies, joint injections, and nerve blocks considered.