Successful opioid therapy often depends on achieving a balance between analgesic effectiveness and side effects. The risk of opioid-induced cognitive impairment often hinders clinicians and patients from initiating or optimizing opioid therapy. Despite subjective experiences of mental dullness and sedation, objective tests of cognitive functioning do not always demonstrate marked changes following opioid administration. To guide clinical practice, as well as patient and family teaching, pain management nurses should be familiar with literature regarding this topic. The purpose of this article is to review the empiric literature on opioids and cognitive functioning, including the relationships among pain, cognition, delirium, and opioids. In general, research reflects minimal to no significant impairments in cognitive functioning. If impairment does occur, it is most often associated with parenteral opioids administered to opioid-naive individuals. Some evidence suggests that opioids may actually enhance cognitive function and decrease delirium in some patient populations. This article describes this research and explores the clinical implications of the research in this area.