In this issue of Dermatologic Surgery, Nasser and colleagues1 provide a comprehensive overview of the modalities available to diminish pain associated with botulinum toxin (BTX) injections for treatment of palmoplantar hyperhidrosis (HH). Limited by cost and tolerability, BTX injections are used for HH once patients have failed other modalities such as topical therapies and/or iontophoresis. As discussed in the article, one major limitation of injection therapy, particularly in heavily innervated areas such as the palms and soles, is the significant associated pain experienced by patients during the procedure. When treating palmoplantar hyperhidrosis, sub-dermal injections are placed in a grid-like fashion on the palms and soles, requiring between 20 and 40 injections per hand or foot. And although a variety of efforts have been used to reduce pain during injection, there is a lack of consensus and quality of evidence for these methods. Most publications in the medical literature are expert opinions and studies with severe limitations, as opposed to prospective, randomized, controlled trials. In this article, the authors highlight the pros and cons of each pain control method including the degree of invasiveness, duration of postprocedure impairment, local adverse side effects, time necessary to achieve anesthesia, and requirement of prior training. A reasonable approach for a practitioner is to first implement a less invasive method such as cooling and/or topical anesthesia. If this does not result in adequate pain control for a patient, a more invasive method may be pursued such as a nerve block or Bier's block (which would require significant prior training).