Nicotine and its pharmacology have long been associated with schizophrenia and its epidemiology and treatment. Schizophrenics use nicotine in its major delivery form of cigarettes at a significantly higher incidence than the general population (80–90% vs. 25–30% of the general population) and even than those diagnosed with other psychiatric diseases. Various studies have demonstrated that cigarette smoking transiently restores cognitive and sensory deficits in patients with schizophrenia/schizoaffective disorders. Conversely, smoking cessation appears to exacerbate the symptoms of the disease. A disturbance of nicotinic receptor expression, affecting the α7 and α4β2 subunits, in various cerebral areas has been revealed in postmortem binding studies. Genetic linkage studies have also demonstrated that the α7 subunit is involved in the pathology of schizophrenia. Much of the drug discovery and development efforts in the nAChR field have focused on α7 and α4β2 nAChR subtypes. These include studies using nicotine and varenicline (the smoking cessation drug marketed as Chantix or Champix) as well as numerous other small-molecule therapeutics targeting these receptor subtypes. While some early studies included α4β2 modulators, the large majority of drug development of nAChR ligands for schizophrenia have been α7 agonists and partial agonists. Such therapeutics are in late-stage development and may constitute a breakthrough for the treatment of schizophrenia with safe and effective medicines.