Schizophrenia is a chronic, severe, and disabling mental illness affecting approximately 2.5 million Americans. Despite enormous efforts made by scientists, the precise etiology of schizophrenia remains largely unknown todate. Interestingly, many lines of evidence over many years have revealed a high prevalence of smoking in patients with psychiatric illnesses, especially schizophrenia. Preclinical and clinical studies indicate that both α7-nicotinic acetylcholine receptors (α7-nAChRs) and β2*-nAChRs play a role in the pathogenesis of schizophrenia. This review emphasizes evidence of linkage between nAChRs and schizophrenia and potential therapeutic applications of α7-nAChR agonists and β2*-nAChR agonists in the treatment of schizophrenia.