In this review, we examine the problem of low configurational stability as encountered for a number of chiral drugs and resulting in racemization or epimerization. The focus is on implications in medicinal chemistry and drug research. When configurational stability is truly low and results in half-lives of racemization or epimerization in the order of minutes or hours, the phenomenon has pharmacological significance. When, in contrast, the half-lives of racemization or epimerization are in the order of months or years, the phenomenon has pharmaceutical significance and may shorten the shelf-live of the drug. A fast method exists to determine the configurational stability of drug candidates having a chiral centre of the type R '' R'RC-H, namely proton-deuterium exchange. The reaction has the considerable advantage that it can be performed with the racemate. In other wards, it allows chiral drug candidates to be screened for configurational stability prior to their resolution. A qualitative estimate of configurational stability is feasible, since the substituents around the chiral carbon play a determining role in stabilizing or destabilizing the configurational stability of chiral carbons. In contrast, a quantitative prediction of rates of racemization appears practically impossible at present in view of the marked influence of salvation effects. Many examples indicate a mechanism of general-base catalysis in reactions of isomerization. The pharmacological implication is that racemization or epimerization of chiral compounds in biological media can be expected to be catalyzed by a variety of endogenous buffers such as plasma proteins, amines, and perhaps thiolates, phosphate and bicarbonate. Thus, it will not be possible to deduce rates of in vivo chiral inversion of drugs from results obtained in non-biological media. Only experiments conducted in vivo or in biological media such as blood plasma will yield clinically useful figures for racemization or epimerization of configurationally labile chiral drugs