Lung cancer is the second most common cancer and the most lethal cancer worldwide. Melatonin, an indoleamine produced in the pineal gland, shows anticancer effects on a variety of cancers, especially lung cancer. Herein, we clarify the pathophysiology of lung cancer, the association of circadian rhythm with lung, and the relationship between shift work and the incidence of lung cancer. Special focus is placed on the role of melatonin receptors in lung cancer, the relationship between inflammation and lung cancer, control of cell proliferation, apoptosis, autophagy, and immunomodulation in lung cancer by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as a comprehensive reference for the various mechanisms of action of melatonin against lung cancer, as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for lung cancer.