Aesthetic use of botulinum toxin (BoNT) has expanded greatly beyond conventional low-dose (20 U) treatments, leading to some patients receiving doses previously reserved for therapeutic uses. The resulting risks are compounded in patients who receive BoNT for both aesthetic and therapeutic indications. Implementing tools for risk management is a high priority to prevent reduced treatment duration and effectiveness. To highlight the immunogenic risks of higher doses, with special attention to the compounding risks of resistance in patients with overlapping BoNT treatments from aesthetic and therapeutic indications. Authors examined the literature on current practices to provide a side-by-side comparison of BoNT doses for aesthetic and therapeutic indications. Aesthetic BoNT doses used in combination treatments of multiple areas or single treatments of large muscle areas can meet or exceed those observed in therapeutic treatments. Physicians have a responsibility to incorporate risk management and open dialog into their BoNT treatment plans to maximize effectiveness and longevity of treatments.