Background: Botulinum toxin has a well-defined role among dermatologists for the treatment of facial wrinkling, brow position, and palmar and axillary hyperhidrosis. Objective: The purpose of this study is to educate dermatologists on the pharmacology of botulinum toxin. Methods: A retrospective review of the literature on botulinum toxin from 1962 to the present was conducted. We examined the clinical applications of botulinum toxin, cholinergic neuromuscular transmission, the toxin’s structure and molecular actions, drug and disease interactions at the neuromuscular junction, toxin assays, determinants of clinical response, and adverse side effects. Results: Botulinum toxin blocks the release of acetylcholine from the presynaptic terminal of the neuromuscular junction. Several drugs and diseases interfere with the neuromuscular junction and the effects of botulinum toxin. The mouse bioassay, the most sensitive and specific measurement of toxin activity, is the gold standard for botulinum toxin detection and standardization. The major determinants of clinical response to treatment are the toxin preparation, individual patient’s anatomy, dose and response relationships, length of toxin storage after reconstitution, and immunogenicity. To minimize potential antibody resistance, one should use the smallest effective dose, utilize treatment intervals of more than 3 months, and avoid booster injections. Uncommon adverse effects include ptosis, ectropion, diplopia, bruising, eyelid drooping, hematoma formation, and temporary headaches. Conclusion: Botulinum toxin is a safe and effective treatment. Knowledge of the pharmacologic basis of therapy will be useful for standardizing techniques and achieving consistent therapeutic results in the future. (J Am Acad Dermatol 2000;43:249-59.)