Reliable diagnosis of respiratory infection due to Chlamydia pneumoniae and investigation of its role in chronic diseases remain difficult because of the absence of well-standardized and commercially available diagnostic tests. In 2001, the US Centers for Disease Control and Prevention published recommendations for standardizing the diagnostic approach. In this review, we discuss the current state of knowledge of C. pneumoniae-associated respiratory infections in the context of epidemiological studies published during the past 5 years, with particular emphasis on the diagnostic strategies used and their impact on results. The single most likely factor underlying wide variations in data is the significant interstudy variation of the choice of diagnostic methods and criteria used. Adoption of a more unified approach, both for choices of diagnostic methods and for validation of new molecular assays, is long overdue and will be critically important for development of a standardized test for clinical laboratories.