Adrenergic signaling is important for the retrieval of intermediate-term contextual and spatial memories. The role of norepinephrine in retrieval requires signaling through beta1-adrenergic receptors in the hippocampus. Environmental cues activate the locus ceruleus, the main adrenergic nucleus of the brain, when an environmental stimulus is memorable. This leads to norepinephrine activation in the hippocampus, which is important for retrieving memories. Although beta-blockers do not impair cognition in normal subjects, this article explores the possibility that central nervous system (CNS)-active beta-blockers could affect delayed memory in patients with cognitive impairment. The authors investigated the influence of beta-blockers on delayed memory function in cognitively impaired patients. There was a trend for worse delayed memory retrieval in patients who were on CNS-active beta-blockers. These data support the notion that common medications used in cognitively impaired elderly patients can worsen cognition and that careful selection of medications may help to maximize retrieval of newly formed memories.