Synthetic chemistry relies heavily on organic solvents which are often toxic and hazardous as well as expensive in purchase and disposal. The application of water as an alternative reaction medium is not only advantageous from an environmental and safety perspective but can also offer improved selectivity and reaction rates. The exploration of this new, sustainable approach comes along with an ever-growing spectrum of reaction procedures. In this current opinion, we provide an overview of a new methodology that uses a polymeric cellulose derivative, hydroxypropyl methylcellulose, to enable chemical reactions in water.