Tobacco addiction among persons with serious mental illness (SMI) has been largely ignored. About 75 to 85% of persons with schizophrenia, bipolar disorder, and other SMI use tobacco; most will either die and/or have reduced quality of life because of tobacco-caused medical diseases. Tobacco addiction is the most common co-occurring disorder for the SMI population. A dramatic reduction in tobacco use in the general population has occurred during the past 40 years; however, there has been almost no reduction for smokers with SMI. The University of Medicine and Dentistry of New Jersey program targets smokers with SMI and provides outreach services, clinical treatment and research, and consultation to other community-based mental health treatment agencies in New Jersey. Clinical and research evidence supports motivation-based treatment, blending mental health and addiction treatment approaches, and integrating tobacco dependence treatment within mental health settings. The unique barriers and clinical issues for this population are described.