By conducting a systematic review, Mehra et al assessed the impact of marijuana smoking on the development of premalignant changes in the lung and lung cancer. The resulting 19 studies included in the review found an association of marijuana smoking with increased tar exposure, alveolar macrophage tumoricidal dysfunction, increased oxidative stress, and bronchial mucosal histopathologic abnormalities compared with tobacco smokers or nonsmoking controls. Observational studies of subjects with marijuana exposure failed to demonstrate significant associations between marijuana smoking and lung cancer after adjusting for tobacco use. The primary methodological deficiencies noted include selection bias, small sample size, limited generalizability, overall young participant age precluding sufficient lag time for lung cancer outcome identification, and lack of adjustment for tobacco smoking. Given the prevalence of marijuana smoking and studies predominantly supporting biological plausibility of a marijuana smoking–lung cancer association on the basis of molecular, cellular, and histopathologic findings, physicians should advise patients regarding potential adverse health outcomes until further rigorous studies are performed allowing definitive conclusions.