We have examined how nicotine exposure from smoking affects hormonal levels and metabolic homeostasis, using information from both humans and animal studies. The effect of smoking in thyroid disease, osteoporosis, and lipid levels has also been discussed. With the high prevalence of smoking throughout the world and the growing burden of diabetes, smoking cessation of patients should be actively pursued as part of prevention and management of diabetes regiments. However, the challenge of weight gain following smoking cessation remains, and this current review points out the impact of underlying hormonal changes, as well as the psychological factors that are associated with this weight gain. Furthermore, as smoking by pregnant women continues, hormonal changes in response to nicotine exposure might gravely impact upon fetal health, and thus smoking cessation is highly recommended.