One of the enantiomers of a racemic drug may be pharmacologically inactive or toxic or ballast and, hence, U.S. FDA and European agencies have issued certain guidelines for marketing of optically active (homochiral) drugs. However, some homochiral drug enantiomers racemize in to human body leading to the generation of other antipodes, which may be toxic or ballast to the human beings. In addition, racemization reduces the administrated dosage concentration when the optically active enantiomer is converted into its inactive form. Therefore, racemization studies of homochiral drugs are the important and urgent need of today. This article reviews in vitro and in vivo racemization of homochiral drugs. The racemization of some homochiral drugs is described considering the affect of different variables such as temperature, concentration of the drug, ionic concentration, pH, addition of cyclodextrins, formation of inclusion complexes, etc. Efforts have also been made to discuss the mechanisms of the racemization process. Attempts have been made to suggest safe dosages of such drugs.