Botulinum toxin (Botox) has been recommended as one option for management of refractory clozapine-induced salivation (sialorrhea). Since 2004, there has been a growing evidence base on botulinum toxin for clozapine-induced sialorrhea. There is evidence prior to this for other conditions, such as sialorrhea related to Parkinson’s disease, for which there have been multiple randomized controlled trials. Botulinum toxin injections into the bilateral parotid and submandibular salivary glands prevent the release of acetylcholine from axon endings, halting the release of saliva. Injections of Botox have onset within 4 days and last 3 to 6 months. Side effects are infrequent and include increased saliva thickness, dysphasia, dry mouth and pneumonia. An advantage of using botulinum toxin is that it does not create the anticholinergic burden of other more commonly used medications, such as ipratropium, atropine, glycopyrrolate, terazosin, amitriptyline, scopolamine, clonidine, and guanfacine. Botulinum toxin is an effective option for managing clozapine-induced sialorrhea. Clinicians can consider Botox before some other medications with more burdensome side effect profiles. If the clinician has not been trained in botulinum toxin injection, they will need to refer the patient to a practitioner who is skilled in the use of botulinum toxin.