The majority of patients with reported penicillin allergy are not allergic when tested or challenged. Penicillin allergy testing has been shown to significantly reduce annual healthcare expenditures. Data have emerged showing β-lactams have multidimensional antibacterial effects in vivo, far beyond what is appreciated in standard bacteriological susceptibility testing media. These include enhancing bacterial killing by the innate immune system. Supporting the clinical relevance of these secondary underappreciated effects are recent clinical and pharmacoeconomic analyses that show worse outcomes in patients with reported penicillin allergies who receive non-β-lactam antibiotics when compared to their non-penicillin-allergic counterparts. This is particularly relevant in the treatment of Staphylococcus aureus bacteremia. This article reviews the tremendous advantages offered by β-lactam therapy and makes a strong case that the debunking of false penicillin allergies through a detailed allergy history and penicillin allergy testing should be a vital component of antimicrobial stewardship practices.