This paper shows the versatility of modified charged and uncharged β-cyclodextrins (CDs) in the direct chiral resolution of β-agonists, β-antagonists, phenylethyamines and alcohol stimulants, and thalidomide and its metabolites. A total of 42 compounds were optically resolved using hydroxypropyl-β-CD and 20 with sodium sulfobutyl ether-β-CD. The degree of enantiomeric separation for most substances is dependent on the modified CD concentration. The separation efficiency reaches a maximum at a particular CD concentration. The separation efficiency reaches a maximum at a particular CD concentration, after which further increases in CD concentration causes a progressive decrease in chiral differentiation. Chiral separation of amphetamine enantiomers indicated that a three-point hydrogen bond interaction between the chiral guest molecule and host CD is not necessary for chiral separation under the conditions used.