Nicotine replacement therapies (NRT) were the main pharmacologic option for treatment of nicotine dependence until the early 1990s, when controlled clinical trials confirmed the efficacy of bupropion, the first treatment not based on nicotine. Varenicline, a partial agonist at nicotine receptors, gained US regulatory approval in 2006 for smoking cessation. Although these agents are all effective for nicotine dependence, their efficacy rates vary compared with placebo (overall OR for NRT efficacy, 1.77; for bupropion, 1.94; for varenicline, 3.09). Each of these treatments has a place, sometimes in combinations with other agents, in cancer patients who continue to smoke. Our initial experience with varenicline has been encouraging. Bupropion has specific advantages for cancer patients, including increased energy, low risk for nausea, and decreased weight gain from quitting.