A number of reports including a recent publication in Osteoarthritis and Cartilage have suggested that smokers have a lower than expected prevalence of osteoarthritis (OA) than nonsmokers. We review the evidence linking smoking with OA, suggest approaches whereby the direct and indirect effects of smoking on OA might be distinguished, highlight two diseases, ulcerative colitis and Parkinson's disease, where smoking is protective, discuss mechanisms by which nicotine might act and lastly explore the association of smoking with enhanced musculoskeletal pain.