Explore a comprehensive review of groundbreaking clinical microbiology research from 2020, focusing on the challenges and innovations brought about by the COVID-19 pandemic. Delve into discussions by three Journal of Clinical Microbiology editors as they highlight nine influential papers, covering topics such as SARS-CoV-2 testing methods, blood culture utilization during the pandemic, artificial intelligence applications in diagnostics, metagenomics for pathogen detection, and antimicrobial resistance. Gain insights into the rapid development of COVID-19 diagnostics, including saliva-based tests and portable sequencing platforms, as well as advancements in detecting tick-borne pathogens and analyzing cerebrospinal fluid. Learn about the correlation between neutralizing antibodies and COVID-19 protection, and understand the global spread of antibiotic resistance in Streptococcus pyogenes.