There are many side effects of opioids used for cancer and non-cancer pain, which can limit their use and vastly undermine the quality of life for patients. Sedation is a frequent and serious side effect of opioid analgesics, sometimes reported as fatigue or tiredness from patients. There are a number of specific therapies to control or manage these adverse effects, making it feasible to dose opioids to adequate analgesia with tolerable side effects. The balance between effect and side effects is the goal of chronic opioid pharmacotherapy. In particular, sedation commonly can be problematic in a patient who is taking opioids, to the extent that one may want to discontinue the medication and suffer with the pain rather than experience debilitating fatigue or sedation. When sedation clinically becomes excessive, measures should be taken to make it possible to continue treatment with analgesics with acceptable sedation management. There are many techniques to oppose sedation including simple antidotes, such as rest, exercise, and timing of opioid medications, and more complex solutions, such as opioid rotation and the use of psychostimulants or other classes of medications to counteract sedation. The treatment of opioid-induced sedation can be very effective and should be part of a skill set that the clinician can easily employ to enhance the quality of life of patients.