Botulinum toxin (Botox) produced by Clostridium botulinum is a potent neuromuscular blocker agent that inhibits acetylcholine release from presynaptic nerve endings. This effect was confirmed in the smooth muscle of the gastrointestinal tract and led to clinical trials investigating the efficacy of Botox for treatment of several gastrointestinal disorders. Multiple controlled studies have shown that Botox is effective in short-term management of achalasia. Botox reduces lower esophageal sphincter pressure, improves esophageal clearance, and alleviates symptoms in up to 70% of patients; however, its long-term efficacy decreases to 30% and repeated injections are often necessary. Botox is reserved for older patients and with high surgical risk. The main predictors of a good response are older age and presence of vigorous achalasia. Biliary or pancreatic sphincter of Oddi dysfunction (SOD) has been another indication for Botox administration. Transendoscopic injection of Botox in the papilla of Vater has shown relief of symptoms in more than 50% of cases of SOD. Furthermore, a Botox clinical response in this condition can predict a long-term benefit with endoscopic sphincterotomy. Botox decreases resting anal pressure, has healing rates of approximately 80% at six months after injection in patients with chronic anal fissure, and has a better outcome than topic nitroglycerine. Case reports have shown good results with Botox administration in treatment of diffuse esophageal spasm, anismus, oropharyngeal dysphagia, anterior rectocele, and secondary achalasia. Administration of botulinum toxin has a low rate of adverse reactions and complications.