Mycoplasma pneumoniae-associated pericarditis may result in pronounced morbidity unless appropriate therapy is administered. In this report, we describe a patient who had recurrent episodes of chest pain, intermittent constitutional symptoms, and, eventually, cardiac tamponade due to pericarditis despite treatment with nonsteroidal anti-inflammatory drugs. Immunofluorescence antibody titers were consistent with recent M. pneumoniae infection, and antibiotic therapy resulted in rapid and complete resolution of the patient's symptoms. This treatable entity may be underrecognized and can now be diagnosed with sensitive serologic testing.