Mycobacterium fortuitum is classified as a rapidly growing mycobacterium (RGM) according to the Runyon classification. RGM are increasingly being recognized as human pathogens. Joint infection due to M. fortuitum is a rare, but serious disease. This report describes a patient with acquired immunodeficiency syndrome (AIDS) and septic arthritis of the knee due to M. fortuitum in a previously normal joint with no history of surgery or intra-articular injections.