The emergence of beta-lactam–resistant pathogenic organisms has resulted in limitation or even elimination of drugs such as penicillin and ampicillin from available antibiotic choices for treating common infections in obstetrics and gynecology. In clinical situations for which penicillins and cephalosporins are appropriate or recommended first-line agents, the problem of patient-reported penicillin allergies has led to routine use of alternative but potentially less effective agents. The use of broader-spectrum and potentially suboptimal alternative antibiotic regimens for intrapartum antibiotic prophylaxis against group B streptococcus or for surgical prophylaxis for cesarean delivery in women with a reported penicillin allergy may affect these women during labor and birth. Most individuals who report a penicillin allergy are neither truly allergic nor at risk of developing a hypersensitivity reaction after exposure to penicillin. The available evidence suggests that there are important roles for both targeted history-taking, to determine the nature of drug allergies and penicillin allergy testing in pregnant women, to optimize their antibiotic-related treatment both during pregnancy and for their lifetimes. Wider consideration and adoption of penicillin allergy testing in pregnant women specifically, as well as the general population of women cared for by providers of obstetrics and gynecology, is recommended.