The introduction of rapid diagnostic testing has transformed the practice of infectious diseases, facilitating earlier pathogen identification and optimization of antimicrobial therapy. Rapid diagnostic panels have also created new challenges in the interpretation of increasing numbers of results of unclear clinical significance. We highlight the clinical implications of the increasing use of rapid diagnostic panels in pediatric infectious diseases, focusing on commonly adopted testing for the diagnosis of meningitis and encephalitis, bloodstream infections, gastrointestinal infections, and respiratory infections. Rapid diagnostic panels can be useful adjuncts to conventional culture methods, but results must be interpreted with caution and careful attention to the clinical scenario. They are most likely to be successful when implemented in conjunction with clinical guidance in collaboration between microbiology laboratories and antimicrobial stewardship programs.