Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the contemporary practices of sedation providers and anesthesiologists. Reversal or “antidote” drugs, such as flumazenil and naloxone, are often used in unintentional overdose situations involving significant benzodiazepine- and/or opioid-induced respiratory depression. Within the context of skeletal muscle relaxation, neostigmine and sugammadex are routinely used to reverse the effects of nondepolarizing neuromuscular blocking agents. In addition, the alpha-adrenergic antagonist phentolamine is used in dentistry as a local anesthetic reversal agent, decreasing its duration of action by inducing vasodilation. This review article discusses the pharmacology, uses, practical implications, adverse effects, and precautions needed for flumazenil, naloxone, neostigmine, sugammadex, and phentolamine within the context of sedation and anesthesia practice for dentistry.