Tobacco dependence among individuals with a mental illness or an addiction is a tremendous problem that goes largely ignored. Studies of genetics, neuroimaging, and nicotinic receptors support a neurobiological link between tobacco use and alcohol dependence, drug dependence, schizophrenia, depression, attention-deficit hyperactivity disorder (ADHD), and anxiety disorders. This paper summarizes the recent literature on this topic and discusses how treatment for tobacco can no longer be ignored in mental-health and addiction-treatment settings. More research is needed as well as a national organized effort to address tobacco in this large segment of smokers.