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Active smoking is considered a risk factor for rheumatoid arthritis. Smokers show respiratory extra-articular manifestations and complications, such as interstitial lung disease and chronic obstructive pulmonary disease. Smokers may receive a more intensive drug therapy than non-smokers, but they have a poor prognosis. Smoker’s resistance to therapy may be caused by the pharmacokinetic interactions between drugs and tobacco constituents. The present account of some of those thousands of components of the gas and tar phase of cigarette smoke (polynuclear aromatic hydrocarbons, quinones, cyanide, heavy metals, bacterial endotoxins, nicotine and carbon monoxide) may help explain the inconclusive incrimination of tobacco use in the development of rheumatoid arthritis and convince more clinicians to recommend smoking cessation.