Exposure to Artificial Light at Night (ALAN) has been associated with disruption of the circadian system, which has been pointed out to have detrimental effects on health. Exposure to outdoor ALAN is very frequent in industrialised countries due to nocturnal light pollution and the relevant involvement of the total workforce in shift work and night work. Ecological and epidemiologic studies highlight the association between exposure to ALAN and several diseases, mainly obesity and cancer. More recently, also indoor ALAN exposure has been investigated. Among several multifactorial mechanisms linking ALAN exposure and health risks, suppression of melatonin secretion plays a pivotal role leading to alterations in circadian rhythm patterns that are detrimental in terms of appetite regulation and dysfunctions in metabolic signalling and cell growth in cancer. In addition, gut dysbiosis, inflammation, hypovitaminosis D, imbalance in cytokine secretion and levels are responsible for the multiple relationship linking circadian dysregulation due to ALAN exposure and obesity, and cancer. Therefore, the current manuscript summarises human and basic studies pointing out the impact of ALAN exposure on health, mostly focusing on obesity and cancer. Based on extant evidence, prevention strategies for obesity and cancer should be prompted, targeting exposure to ALAN. In recent years, artificial light at night (ALAN) emitted by residential areas, road illumination and non-stop economic activities has been recognised as one of the major and novel risk factors for obesity, with trends in nocturnal light pollution paralleling demographic trends in obesity. Analogous associations emerged between ALAN and certain types of cancer. In urban settings, an increase in ALAN exposure and especially an increase in the blue light spectrum emissions have been observed due to a switch to the use of white light emitting diode technology as the new urban light standard. In addition to light emitting diode lighting, artificial light encompasses different types of illuminating sources, i.e. fluorescent or incandescent lights. Though all these types of artificial light are perceived as white by the retina, they are different technologically speaking and in terms of electromagnetic spectra. Notably, this heterogeneity is responsible for variability in the entrainment of the circadian clock. Indeed, the relevance of ALAN to health is mainly due to its interference with the circadian system. Ambient light, through its spectral composition, is the most relevant ‘zeitgeber’ (namely, an environmental cue able to synchronise the endogenous rhythm) of the circadian system. The wavelength of light, perceived by the eye photoreceptor, triggers the first step in circadian modulation. The retina input reaches the SNC that orchestrates the peripheral clocks by endocrine regulation (mainly through 5-methoxy-N-acetyltryptamine-melatonin and cortisol) or through the autonomic nervous system. Furthermore, the wavelength captured by the skin, by the ultraviolet (UV)-sensitive photopigment neuropsin (ÊŽmax = 380 nm), regulates directly skin clocks. The link seems to be mediated by melatonin. Another pivotal player in this scenario is represented by melatonin. Melatonin is secreted by the pineal gland during the biological night, following the retina stimulations of a specific photoreceptor named melanopsin, different from rods and cones, and sensitive to blue light. ALAN exposure may suppress melatonin production and blunt its circadian rhythmicity through sleep pattern disruption and reduction of sleep duration.