Approximately 30% of all cancer deaths in the United States are caused by tobacco use and smoking. Cancers of eighteen sites have been causally linked to smoking, the most common of which are the lung, head and neck, bladder, and esophagus. While quit rates and quit attempt rates are relatively high shortly after a cancer diagnosis, the recidivism rates are also high. Therefore, screening, treating, and preventing relapse to tobacco use is imperative among patients with and survivors of cancer. To date, research has consistently shown that a combination of pharmacologic and behavioral interventions is needed to achieve the highest smoking cessation rates, with a recent emphasis on individualized treatment as a most promising approach. Challenges in health care systems, including the lack of appropriate resources and provider training, have slowed the progress in addition to important clinical considerations relevant to the treatment of tobacco dependence (eg, a high degree of comorbidity with psychiatric disorders and other substance use disorders). However, continued tobacco use has been shown to limit the effectiveness of major cancer treatments and to increase the risk of complications and of developing secondary cancers. The authors recommend that oncology providers screen all patients for tobacco use and refer users to specialized treatment when available. Alternatively, oncology clinicians can provide basic advice on tobacco use cessation and pharmacotherapy and/or referral to outside resources (eg, quitlines). Herein, the authors summarize the current knowledge on tobacco use and its treatment, with a focus on the related available evidence for patients with and survivors of cancer.