Molecular tools have enhanced our understanding of the epidemiology of infectious diseases by describing the transmission system, including identifying novel transmission modes and reservoirs, identifying characteristics of the infectious agent that lead to transmission and pathogenesis, identifying potential vaccine candidates and targets for therapeutics, and recognizing new infectious agents. Applications of molecular fingerprinting to public health practice have enhanced outbreak investigation by objectively confirming epidemiologic evidence, and distinguishing between time-space clusters and sporadic cases. Clinically, moleculartools are used to rapidly detect infectious agents and predict disease course. Integration of molecular tools into etiologic studies has identified infectious causes of chronic diseases, and characteristics of the agent and host that modify disease risk. The combination of molecular tools with epidemiologic methods provides essential information to guide clinical treatment, and to design and implement programmes to prevent and control infectious diseases. However, incorporating molecular tools into epidemiologic studies of infectious diseases impacts study design, conduct, and analysis.