Clinical Background: Although chronic kidney disease (CKD) and smoking are both associated with high rates of morbidity and mortality, the interplay between the two is not widely understood. Epidemiology: The incidence of CKD progression has been shown to be significantly higher among current and former smokers, and continued smoking thereafter has been associated with a nearly twofold higher risk of death. Challenges: Because it is a silent disease, CKD is often diagnosed in advanced stages, which underscores the importance of targeted, active screening for CKD. When CKD progresses to stage 5, life expectancy is drastically shortened unless life-saving renal replacement therapy (dialysis or kidney transplantation) is initiated. The treatment of smoking, which is a risk factor for CKD, also poses a challenge. Less than 10% of adults who want to quit smoking succeed in doing so, and those who do quit typically succeed only after making multiple attempts. In addition, many smokers have limited access to smoking cessation services, are unaware of available resources, or have misconceptions about smoking cessation therapies. Prevention and Treatment: There is evidence that quitting smoking may help prevent the development of CKD. However, glomerular filtration rates have been found to be higher in smokers than in nonsmokers, which could confound efforts to recognize smoking as a major risk factor for kidney disease. Efforts should continue to focus on the prevention of smoking, and nephrologists should promote smoking cessation as a means to prevent CKD progression.