Group B streptococcus is the leading cause of early-onset neonatal sepsis in the United States. Universal screening is recommended for pregnant women at 35 to 37 weeks' gestation. The Centers for Disease Control and Prevention recently updated its guideline for the prevention of early-onset neonatal group B streptococcal disease. The new guideline contains six important changes. First, there is a recommendation to consider using sensitive nucleic acid amplification tests, rather than just routine cultures, for detection of group B streptococcus in rectal and vaginal specimens. Second, the colony count required to consider a urine specimen positive is at least 104 colony-forming units per mL. Third, the new guideline presents separate algorithms for management of preterm labor and preterm premature rupture of membranes, rather than a single algorithm for both conditions. Fourth, there are minor changes in the recommended dose of penicillin G for intrapartum chemoprophylaxis. Fifth, the guideline provides new recommendations about antibiotic regimens for women with penicillin allergy. Cefazolin is recommended for women with minor allergies. For those at serious risk of anaphylaxis, clindamycin is recommended if the organism is susceptible [corrected] and vancomycin is recommended if there is clindamycin resistance or if susceptibility is unknown. [corrected]. Finally, the new algorithm for secondary prevention of early-onset group B streptococcal disease in newborns should be applied to all infants, not only those at high risk of infection. The algorithm clarifies the extent of evaluation and duration of observation required for infants in different risk categories.