Studies of thermodynamic properties (stability, solubility) are crucial in understanding and explaining drug pharmacokinetic properties and behavior during preclinical studies using in vitro and in vivo models. Tautomers are characterized using traditional spectroscopy and crystallography (X-ray) methods. Broad band spectroscopy has been instrumental in studying the behavior of tautomers in solid crystal, amorphous, and glass phases of drugs. Most drugs are represented commonly using structure determined by the X-ray method, which may be incorrect as there are many cases where the tautomer of the drug in the solid is different from the tautomer in the aqueous phase or other solvents. This tautomer seen in aqueous solution may furthermore be different under different physiological conditions.