Nicotine, the major component of cigarettes, has demonstrated conflicting impact on the immune system: some authors suggest that increases pro-inflammatory cytokines and provokes cellular apoptosis of neutrophils, releasing intracellular components that act as auto-antigens; others claimed that nicotine has a protective and anti-inflammatory effects, especially by binding to 7 subunit of nicotinic acetylcholine receptors. The cholinergic pathway contributes to an anti-inflammatory environment characterized by increasing T regulatory cells response, down-regulating of pro-inflammatory cytokines and a pro-inflammatory cells apoptosis. The effects of nicotine were studied in different autoimmune disease, as multiple sclerosis, type 1 diabetes, rheumatoid arthritis, sarcoidosis, Behc¸ et’s disease and inflammatory bowel diseases. The major problems about nicotine are the addiction and the adverse effects of related to each commercialized formulation. We sought in this review to summarize the knowledge accumulated to date concerning the relationship between nicotine and autoimmunity.