Abstract--Opioid overdose is a potentially life-threatening condition that requires immediate medical attention, often landing affected individuals into the emergency department. The longstanding treatment for opioid overdose has been naloxone, a pure opioid antagonist that reverses all signs of opioid intoxication. While effective as a reversal agent, naloxone has a half-life which is shorter than all opioids. Once the effect of naloxone wears off, patients may experience recurrence of opioid intoxication and the consequences can be fatal. The objective of this article is to review the available literature that addresses routes of administration and doses of naloxone as well as the necessary duration of observation when treating patients who present with opioid overdose. The preferred route of administration remains intravenous with intramuscular and intranasal considered alternatives. Recommended dosing is dependent upon history and the opioid being reversed; however, doses range from 0.05 -2 milligrams. A literature search revealed a relatively small number of studies related to observation periods following naloxone administration and subsequent recurrence of opioid toxicity. The available literature supports incorporation of a two-hour observation period following administration of naloxone for short-acting opioids and a longer four to six hour observation period for reversal of long-acting opioids.