Many innovative and effective smoking-cessation treatments, both behavioral and pharmacologic, have been developed over the past several decades. However, these treatments traditionally have been developed for use with populations of healthy smokers. Despite the disease management implications, efforts to design and evaluate cessation interventions targeting smokers diagnosed with chronic diseases are reported infrequently in the literature. The purpose of this paper is to provide a brief over-view of the evidence linking continued smoking to disease progression and adverse treatment outcomes across a range of common chronic diseases: cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), diabetes, asthma, cancer, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Where studies are available, the efficacy of smoking-cessation interventions specifically developed or applied to these patient populations is reviewed. Finally, limitations and gaps in smoking research and treatment with chronically ill patients are discussed, and future research priorities are recommended.