The use of the neutron diffraction isotope substitution tirst difference method to studying the hydration of molecules in solution is discussed with particular reference to a solution of 2 molal urea in D,O. The structure of the molecule in solution can be determined and refined, and information obtained on the hydration of the. polar amino and carbonyl groups. Comparisons with available computer simulation results show that the potential functions used are unable to reproduce the experimental results, and underline the need to develop better descriptions of intermolecular potential functions before simulations on aqueous systems can be considered to be reliable. Some early results using H,O/DIO mixed solvents to try to separate the contributions of the solvent hydrogen and oxygens to the solute-solvent correlation function-nd hence obtain information on the molecular orientations of the solvent-are presented. The possibility of using nitrogen isotope substitution to probe hydration of apolar groups is illustrated with some recent results on a 2 molal solution of tetramethvlammonium chloride. Future prospects for this powerful technique in tackling important problems -in chemistry and biology are outlined