Smokers with diabetes mellitus substantially lower their risks of microvascular and macrovascular diabetic complications, in particular cardiovascular disease, by quitting smoking. However, subsequent post-smoking-cessation weight gain may attenuate some of the beneficial effects of smoking cessation and discourage attempts to quit. Weight gain can temporarily exacerbate diabetes and deteriorate glycemic control and metabolic profile. The molecular mechanisms by which quitting smoking leads to weight gain are largely associated with the removal of nicotine's effects on the central nervous system. This review addresses mechanisms of post-smoking-cessation weight gain, by reviewing the effects of nicotine on appetite, food intake, eating behaviour, energy expenditure, fat oxidation and appetite-regulating peptides. We also highlight correlations between post-cessation weight gain and risk of type 2 diabetes, consequences of weight gain in people with type 2 diabetes and the role of pharmacotherapies, which combine treatment of nicotine addiction and promotion of weight control.