Part of the life cycle of several fish species includes important salinity changes, as is the case for the sea bass (Dicentrarchus labrax) or the Atlantic salmon (Salmo salar). Salmosalar juveniles migrate downstream from their spawning sites to reach seawater, where they grow and become sexually mature. The process of preparation enabling juveniles to migrate downstream and physiologically adapt to seawater is called smoltification. Daily and seasonal variations of photoperiod and temperature play a role in defining the timing of smoltification, which may take weeks to months, depending on the river length and latitude. Smoltification is characterised by a series of biochemical, physiological and behavioural changes within the neuroendocrine axis. This review discusses the current knowledge and gaps related to the neuroendocrine mechanisms that mediate the effects of light and temperature on smoltification. Studies performed in S. salar and other salmonids, as well as in other species undergoing important salinity changes, are reviewed, and a particular emphasis is given to the pineal hormone melatonin and its possible role in osmoregulation. The daily and annual variations of plasma melatonin levels reflect corresponding changes in external photoperiod and temperature, which suggests that the hormonal time-keeper melatonin might contribute to controlling smoltification. Here, we review studies on (i) the impact of pinealectomy and/or melatonin administration on smoltification; (ii) melatonin interactions with hormones involved in osmoregulation (e.g., prolactin, growth hormone and cortisol); (iii) the presence of melatonin receptors in tissues involved in osmoregulation; and (iv) the impacts of salinity changes on melatonin receptors and circulating melatonin levels. Altogether, these studies show evidence indicating that melatonin interacts with the neuroendocrine pathways controlling smoltification, although more information is needed to clearly decipher its mechanisms of action.