Drug discovery can involve screening natural products or synthesizing innovative new compounds, and the process can become more challenging with products that contain one or more chiral centers. These optically active compounds tend to make good drug candidates, however, so they require stereochemically selective assay methods for their analysis. In this article, the authors describe an enantiomer analysis method development strategy that uses a family of highly sulfated cyclodextrins to resolve a diverse array of compounds. They propose this approach as a first step in developing methods for separating enantiomers.