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Welcome to the 29th edition of Nelson’s Pediatric Antimicrobial Therapy, the third edition written during the COVID-19 pandemic, which continues to significantly affect our lives and our practice of pediatrics. Thank goodness that COVID-19 vaccines are available for all children older than 6 months! All the other pediatric infections (particularly viral infections) are now coming back with a vengeance, as all of you are experiencing. We maintain close contact between our American Academy of Pediatrics (AAP) Publishing colleagues and our group of editors, who continue to provide clinical care and conduct research while creating policy for pediatric COVID-19 on both local and national levels. The chapters have all been updated, supported by the medical literature and by our opinions and justifications when the literature does not provide answers. More than 100 new citations and updates to web pages are again provided to support recommendations. The Nelson’s app has continued to evolve, particularly the search functions, under Dr Howard Smart’s direction (he uses the app in his pediatric practice), and it is easier for me to find information on the app than in the print book. Howard wishes to keep improving the app, so if anyone has some thoughts on how we can make it even easier for you to find information, please just let us know at nelsonabx@aap.org. Peter Lynch, senior manager, publishing acquisitions and digital strategy, has been very supportive of the digital presence of Nelson’s, including the app; we are still trying to get the app into some of the most often used electronic medical records (EMRs) so you can look up infections, antimicrobials, and doses while updating a child’s EMR. As new important information becomes available (eg, as new drugs are approved), we share that information with Howard to add to the app and it is periodically “pushed out” to the registered users. We continue to appreciate the ongoing advice of our digitally savvy colleagues, Dr Juan Chaparro (a pediatric infectious disease specialist at Nationwide Children’s Hospital in Columbus, OH) and Dr Daniel Sklansky (a pediatric hospitalist at the University of Wisconsin–Madison), who share their medical informatics expertise with us to improve our digital user experience and who continue to work with Peter to explore options for the app in EMRs. We are quite fortunate to have nationally/internationally recognized editors who are experts in each field contribute to the Nelson’s chapters, both the clinical chapters and the mini-educational chapters on why they picked specific agents within a class to use for therapy. Dr Chris Cannavino (double board certified in hospital medicine and infectious diseases) continues to update his chapter on antibiotic allergies. We continue to work closely with the AAP, and many of us have close connections with the AAP Committee on Infectious Diseases, particularly Dr David Kimberlin, the editor of the Red Book. Although Nelson’s is published by the AAP, it is not actually AAP policy (in contrast to the Red Book), so we are able to share personal observations that may not be possible in an AAP publication that requires approval by the AAP Board of Directors. We continue to provide grading of our recommendations—our assessment of how strongly we feel about a recommendation and the strength of the evidence to support our recommendation (noted in the Table). This is not the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method but certainly uses the concepts on which GRADE is based: the strength of recommendation and level of evidence. As with GRADE, we review the literature (and the most important manuscripts are referenced), but importantly, we work within the context of professional society recommendations (eg, the AAP) and our experience.