Tobacco use is the most common cause of preventable morbidity and mortality in the United States; it accounts for one-third of all cancer deaths and is thought to account for half of preventable cancer deaths. This article describes the Tobacco Treatment Program at a major academic cancer center. Patients and employees may access these services in a number of ways. All current smokers and recent quitters are proactively contacted and invited to participate. Services provided are tailored to the motivational level of individual patients and their immediate medical needs. The treatment pathways we present are based on our experience from the last 10 years in treating more than 5,000 unique patients with around 60,000 patient visits. These pathways include behavioral counseling and pharmacotherapy, including first-line, second-line, and off-label medication use. This article describes the program with the goal of providing guidance and ideas to others who are developing treatment programs and providing treatment to tobacco users.