Acquired methemoglobinemia is a known complication of topical anesthesia during endoscopic procedures. Benzocaine has been implicated in a majority of cases and has been removed from some hospital formularies. However, a lot of uncertainty exists about the risk factors for this uncommon complication. This review attempts to summarize the current knowledge of this condition and describe known risk factors. Anesthetic and patient-specific risk factors are described along with some hypothetical procedure-related factors. Clinicians should identify patients who are at high risk and apply appropriate postprocedure screening. Prospective studies are needed to further our knowledge and improve patient safety.