Mycoplasma pneumoniae is a common cause of upper and lower respiratory tract infections. Pneumonia is the most clinically important manifestation, but tracheobronchitis and various nonspecific upper respiratory tract symptoms are more typically seen in clinical settings. M. pneumoniae can cause pharyngitis with or without concomitant lower respiratory tract involvement, but it is less commonly detected in other upper respiratory conditions such as otitis media, sinusitis, and the common cold. A variety of methods exist for laboratory diagnosis of M. pneumoniae infection, including culture, serology, and the polymerase chain reaction assay, but each has limitations. This article provides a summary of recent studies that have evaluated the role of M. pneumoniae in upper respiratory tract infections; a brief discussion of its cell biology, pathogenic mechanisms, and epidemiology; and recommendations for laboratory diagnosis and management.