Abstract Context Patients with peripheral neuropathic pain (NP) may only achieve partial pain relief with currently recommended first-line oral treatments, which are also associated with systemic adverse events. Topical treatments are currently considered second- or third-line options, but a recent pharmacologic treatment algorithm has called for broader first-line use of these agents. This has highlighted a need to communicate the benefits associated with topical agents, in particular around the efficacy, targeted local action, and limited systemic availability resulting in minimal systemic adverse events and drug-drug interactions. Objectives This review aims to evaluate the evidence base for topical therapies currently used to treat peripheral NP, discuss the evidence comparing these treatments head-to-head with oral standard of care, and evaluate how they fit into treatment regimens in the “real world.” Methods This is a narrative review. Results Two topical treatments are currently licensed: lidocaine 5% medicated plaster (post-herpetic neuralgia) and the capsaicin 8% patch (peripheral NP). When compared head to head with the oral standard of care (pregabalin), the lidocaine 5% medicated plaster provided similar relief of pain associated with post-herpetic neuralgia but did not meet the primary predefined criteria for noninferiority. The capsaicin 8% patch, however, demonstrated noninferior efficacy when compared head-to-head with pregabalin across a wide range of peripheral NP etiologies. Importantly, both treatments demonstrated effective pain relief without the systemic adverse events associated with oral therapies. Conclusion First-line use of topical agents may be of particular benefit in patients where the safety and tolerability of oral therapy is a concern.