The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published from 1965 to 2008 using combinations of the terms octreotide, antidote, sulfonylurea, overdose, poisoning, and toxicity was performed. References from identified articles were reviewed for additional sources. Animal studies, case reports, case series, and randomized controlled trials were evaluated. An animal model of sulfonylurea overdose demonstrates that octreotide reduces the number of refractory sulfonylurea-induced hypoglycemic episodes. Published case reports describe the use of octreotide to prevent recurrent hypoglycemia after sulfonylurea overdose. A retrospective case series demonstrates that administration of octreotide decreases the need for supplemental dextrose boluses as well as hypoglycemic events. Two prospective, controlled trials determined that octreotide and supplemental dextrose increase blood glucose concentrations with fewer hypoglycemic events. Based on animal and human data, there is sufficient evidence to recommend the use of octreotide with supplemental dextrose for the treatment of sulfonylurea-induced hypoglycemia.