Giraffe anesthesia remains a major challenge due to their unique anatomy and physiology, which predisposes them to life-threatening, anesthesia-related complications. Historical verbal and published reports describe the use of several drugs and drug combinations for giraffe anesthesia. The most widely used anesthetic regimens have involved use of opioids alone or in combination with sedatives (e.g., xylazine) or tranquilizers (e.g., azaparone). Current methods for field anesthesia generally involve darting giraffe with very high doses of an opioid (etorphine, thiafentanil or carfentanil) combined with hyaluronidase for rapid induction, and then reversing the opioid as soon as the giraffe is recumbent, to reduce consequences of the opioid overdose. This anesthetic technique greatly limits what can safely be done to a giraffe while it is recumbent. A combination of medetomidine and ketamine is currently considered a safe and reliable alternative to opioid combinations for captive giraffe, but is considered less than optimal for capture of free-ranging giraffe.