Many patients report allergies to penicillin, although in over 90% of these the label of penicillin allergy is shown to be incorrect following comprehensive testing. Inappropriate and inaccurate penicillin allergy labelling is a barrier to antimicrobial stewardship and can lead to patient harm. This review assesses an emergent evidence base and trend favouring delabelling using direct oral penicillin challenges following a stratified risk assessment of the likelihood and existence of true penicillin allergy, to identify and make recommendations for key components for implementation in standard practice. Research to date has focussed on the feasibility and clinical and financial outcomes of these direct delabelling strategies. There is a paucity of studies exploring the views and engagement of patients and healthcare professionals, and a gap in the evidence for prerequisites to safely deliver, sustain and spread the implementation of such services across health systems.