Chlamydia pneumoniae is an obligate intracellular human pathogen responsible for a wide range of acute and chronic human diseases, including pneumonia and other respiratory diseases. Serological methods for the diagnosis of C. pneumoniae infection vary widely, and several authors have reported significant inter- and intra-laboratory variability in diagnostic methods and criteria. Over the past 10 years, numerous studies have focused on the identification of specific antigens for application in serodiagnosis, including the diagnosis of persistent infections. The use of proteomics may enable the development of serological diagnosis kits that offer reliable sensitivity and specificity and might even differentiate between the various stages of infection with this pathogen.