The clinical manifestations of group A streptococcal and nonstreptococcal pharyngitis overlap quite broadly. For this reason, the updated Infectious Diseases Society of America practice guideline for group A streptococcal pharyngitis, published in this issue of Clinical Infectious Diseases, recommends laboratory confirmation of the clinical diagnosis by means of either throat culture or a rapid antigen detection test. However, a recently published guideline, developed by a subcommittee of the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) in collaboration with the Centers for Disease Control and Prevention, advocates use of a clinical algorithm alone, in lieu of microbiologic testing, for confirmation of the diagnosis in adults for whom the suspicion of streptococcal infection is high. In this discussion, we examine the assumptions of the ACP-ASIM guideline, question whether its recommendations will achieve the stated objective of dramatically decreasing excess antibiotic use, and suggest that its recommendations be confirmed by clinical trials before clinicians abandon long-held teachings regarding diagnosis and management of group A streptococcal pharyngitis.