Fish display robust neuroendocrine and physiologic stress responses to noxious stimuli. Many anesthetic, sedative, or analgesic drugs used in other vertebrates reduce stress in fish, decrease handling trauma, minimize movement and physiologic changes in response to nociceptive stimuli, and can be used for euthanasia. But extrapolating from limited published anesthetic and sedative data to all fish species is potentially harmful because of marked anatomic, physiologic, and behavioral variations; instead, a stepwise approach to anesthetizing or sedating unfamiliar species or using unproven drugs for familiar species is advisable. Additionally, knowledge of how water quality influences anesthesia or sedation helps limit complications. The most common method of drug administration is through immersion, a technique analogous to gaseous inhalant anesthesia in terrestrial animals, but the use of injectable anesthetic and sedative agents (primarily intramuscularly, but also intravenously) is increasing. Regardless of the route of administration, routine preprocedural preparation is appropriate, to stage both the animals and the supplies for induction, maintenance, and recovery. Anesthetic and sedation monitoring and resuscitation are similar to those for other vertebrates. Euthanasia is most commonly performed using an overdose of an immersion drug but injectable agents are also effective. Analgesia is an area in need of significant research as only a few studies exist and they provide some contrasting results. However, fish have mu and kappa opiate receptors throughout the brain, making it reasonable to expect some effect of at least opioid treatments in fish experiencing noxious stimuli.