Invasive pneumococcal disease is often associated with an increased incidence of adverse cardiac events. A new study now shows that Streptococcus pneumoniae, the main cause of community-acquired pneumonia, causes direct cardiotoxicity and induces the formation of microscopic lesions within the myocardium of experimentally infected mice. These microlesions had a vacuolar morphology, were filled with pneumococci and lacked infiltrating immune cells. Microlesion formation required interactions between the bacterial choline binding protein A (CbpA) and host laminin receptor, and between the bacterial cell wall and platelet-activating factor receptor (PAFR). In addition, S. pneumoniae pneumolysin was detected in the lesions, and exposure to the purified toxin resulted in the death of cardiomyocytes. Finally, antibodies against CbpA and pneumolysin prevented microlesion formation, which suggests that a pneumococcal vaccine may have the potential to prevent cardiac damage.