Atypical pneumonia is a term applied to lower respiratory tract infections that are not characterized by signs and symptoms of lobar consolidation. This article will discuss the epidemiology, clinical manifestations, and laboratory diagnoses of Mycoplasma pneumoniae, Chlamydia sp., Legionella sp., Francisella tularensis, and Coxiella burnetii, which are the agents most commonly associated with atypical pneumonia. Because many of these pathogens are intracellular, diagnosis depends upon serological confirmation. The current serological tests used to identify these agents in the etiologic diagnosis of atypical pneumonia are described. Recently, however, it has become possible to make a diagnosis directly in these cases using DNA or protein microarrays. Here, we describe the development of a new, automated technique for simultaneous testing and detection of several pathogens using a multiplexed serology test. This should prove to be a valuable tool for the rapid determination of patient status, allowing effective and efficient postexposure prophylaxis and treatment.