The smoking rate for patients with schizophrenia reaches as high as 90% in clinical samples, 70% for patients with bipolar disorder, and 40% to 50% for patients with major depression and anxiety disorders. Because it is a significant health hazard, smoking should be aggressively discouraged, and, in this group of patients, a combination of behavioral therapy and pharmacotherapy currently offers the best option. Nicotine provides a number of benefits, including anxiety relief, increased alertness, and improved cognitive functioning. It alters a wide range of central nervous system neurotransmitters. Unfortunately, nicotine readily establishes physiological dependence. In cessation efforts, transdermal nicotine patches and nicotine gum are helpful adjuncts. The primary FDA approved non-nicotine pharmacotherapy agent is bupropion (Zyban). Studies summarizing the effectiveness (or lack thereof) of other (off-label) agents, such as tricyclic antidepressants, MAO-Inhibitors, SSRIs, and clonidine, are cited.