Community-acquired pneumonia (CAP) is a world wide cause of morbidity and mortality. The etiology of CAP is different between countries and changes over time. With the increasing incidence, atypical pathogens are attracting more and more attention all over the world. In many countries, atypical pathogens are one of the main pathogens of CAP, and even could be the most prevalent etiology in China. Atypical pathogen infections can cause multi-system complications, which leads to a worse prognosis. Although still controversial, empirical antibiotic coverage of atypical pathogens in CAP may improve outcomes, shorten length of hospitalization, reduce mortality and lower total hospitalization costs. The macrolide resistance rate of atypical pathogens, especially Mycoplasma Pneumoniae (M. Pneumoniae) is high, so fluoroquinolones or tetracyclines should be considered as alternative therapy.