The response of Saccharomyces cerevisiae to osmotic stress, whether arising from environmental conditions or physiological processes, has been intensively studied in the last two decades. The well-known high-osmolarity glycerol (HOG) signalling pathway that is induced in response to osmotic stress interacts with other signalling pathways such as the cell wall integrity and the target of rapamycin pathways. Osmotic balance is also maintained by the regulated opening and closing of channel proteins in both the cell membrane and intracellular organelles such as the vacuole. Additionally, environmental stresses, including osmotic shock, induce intracellular calcium signalling. Thus, adaptation to environmental stresses in general, and osmotic stress in particular, is dependent on the concerted action of components of multiple interacting pathways. In this review, we describe some of the major mechanisms and molecules involved in osmoregulation via pathways other than the high-osmolarity glycerol pathway and their known interactions with one another that have been discovered over the last two decades.