Mycoplasma pneumoniae is a highly specialized parasitic bacterium that is a significant cause of community-acquired pneumonia in children. Although most such respiratory infections are mild, a minor percentage of patients require hospitalization and, occasionally, intensive treatment for respiratory failure. A variety of extrapulmonary sequelae of M pneumoniae infections have been described, including Stevens-Johnson syndrome. Macrolide resistance in M pneumoniae has developed rapidly in Asia, particularly in China, over the past decade and is now appearing in the United States. Emerging resistance to macrolides creates a therapeutic conundrum, particularly for pediatricians caring for young children in whom absolute or relative contraindications exist for the use of tetracyclines or fluoroquinolones, the 2 other main classes of drugs shown to be efficacious for M pneumoniae. We describe here the case of a child with a prolonged febrile illness associated with Stevens-Johnson-like mucocutaneous involvement who was found to have a respiratory infection with macrolide-resistant M pneumoniae.