The first edition of the Red Book was published in 1938. Since then, there have been numerous advances in the fields of infectious diseases and public health that have decreased morbidity and mortality of infants, children, and adolescents. Over the years, emerging pathogens and disease complexes have been described, sophisticated diagnostic techniques developed, advances in antimicrobial therapy have occurred, and immunizations have been implemented to prevent previously deadly diseases. Of the 18 diseases or organisms in the 1938 edition, 13 are now vaccine-preventable. Since inception of the Red Book, the aims of the editors have been to keep pace with these innovations and to continue to inform the medical community. These goals have made the Red Book a fundamental resource for pediatricians and other health care professionals in terms of guiding diagnosis, therapy, and prevention of infectious diseases. The list of 18 diseases or organisms originally described in the 1938 Red Book has expanded to include over 160 diseases or organisms in the 2012 edition. The pace of biomedical discovery, as well as the amount of information available and the number of methods for its delivery, will continue to accelerate in the future. Integration of information into future editions of the Red Book will ensure that practitioners continue to rely on the Red Book in its various electronic formats for clinical guidance and support.