Microbial organisms are known to rely for osmotic regulatory purposes on an assortment of low molecular weight molecules earmarked for function as osmolytes. The so‐called ‘compatible’ subclass of osmolyte, notably glycine betaine, is distinguished by a propensity to avoid the large bound fraction of cytoplasmic water adsorbed at the surface of biological macromolecules. Here we argue that this property is implicated in thermodynamic stabilisation of the cytoplasm. A rudimentary molecular statistical approach indicates that flooding the cytoplasm with large amounts of compatible osmolyte is an effective way to deal with the threat of phase separation.