Although tobacco is a well-established causal agent for many human cancers, less emphasis has been placed on translating this evidence by evaluating the effects of continued tobacco use after a cancer diagnosis. A broad assessment of the effects of continued tobacco use demonstrates that tobacco increases cancer treatment toxicity, recurrence, second primary tumors, and mortality in patients with cancer. Few studies report the potential benefits of cessation after a cancer diagnosis, but data suggest improved treatment outcomes in patients with cancer who quit smoking. Improving tobacco cessation treatment efficacy and access to cessation support has been sparsely researched in the oncology setting compared with the general population; however, patients with cancer are receptive to standard evidence-based tobacco cessation guidelines. Several studies demonstrate moderate tobacco cessation success in patients with cancer using the general principles of evidence-based tobacco cessation support. Several systems-level issues and research efforts are needed to standardize tobacco use definitions, increase access to tobacco cessation support, improve tobacco cessation efficacy, understand the time-dependent effects of tobacco and cessation on cancer biology, and realize the potential benefits of tobacco cessation for patients with cancer.