According to the US Public Health Service, all patients attempting to quit smoking should be encouraged to use one or more effective pharmacotherapy agents for cessation except in the presence of special circumstances. This article provides an overview of the pharmacologic agents for acute and critical care nurses to consider when intervening with tobacco-dependent patients. Medications addressed in this article include (1) first-line agents (nicotine replacement therapy, sustained-release bupropion) that have proven efficacy and are approved by the Food and Drug Administration (FDA) for smoking cessation, (2) second-line agents (nortriptyline, clonidine) that have proven efficacy but no FDA indication for smoking cessation, (3) approaches that use of combination or high-dose therapy, (4) herbal therapies, and (5) emerging therapies that are currently under investigation.