Depression is major problem for the medically ill population but few recommendations have been made regarding treatment with specific compounds in many of these illnesses. This review attempts to consider the inter-relationship between smoking, pulmonary disease and mood disorders. It has been reported that nearly 50% of patients with chronic pulmonary illnesses report depressive symptoms at some time during the course of their illness, but with the complex issues regarding respiratory drive and substance dependence, little in the way of specific clinical information have been made for this group. In this review, the theorectical relationship that exists between dopamine, serotonin and nicotine and how the biochemical nicotine dependence issues (with regard to mood) may actually be a key element in the understanding and treatment of depression later in the life of the development of chronic lung disease and depression, are discussed.