Since the early 1980s, there has been growing concern about potential health consequences of exposure to second-hand smoke (SHS). Despite SHS being established as a risk factor for lung cancer development, the estimated risk has remained small yet somehow debatable. Human exposure to SHS is complicated because of temporal variabilities in source, composition, and concentration of SHS. The temporality of exposure to SHS is important for human lung carcinogenesis with a latency of many years. To explore the causal effect of SHS in lung carcinogenesis, exposure assessments should estimate chronic exposure to SHS on an individual basis. However, conventional exposure assessment for SHS relies on one-off or short-term measurements of SHS indices. A more reliable approach would be to use biological markers that are specific for SHS exposure and pertinent to lung cancer. This approach requires an understanding of the underlying mechanisms through which SHS could contribute to lung carcinogenesis. This Review is a synopsis of research on SHS and lung cancer, with special focus on hypothetical modes of action of SHS for carcinogenesis, including genotoxic and epigenetic effects.