We present a comprehensive molecular simulation program package, the Peking University Drug Design System (PKUDDS), which runs on personal computers. PKUDDS has been developed mainly for computer-aided drug design using the methods of two-dimensional quantitative structure-activity relationships, three-dimensional quantitative structure-activity relationships, molecular docking, and database screening. This study presents an overview of its functionality, especially of methods developed in our group. PKUDDS uses genetic algorithms in molecular docking, conformational analysis, and quantitative structure-activity relationships as the most useful optimization technique. A user-friendly graphical interface provides easy access to many functions of PKUDDS. We report some examples of our considerable research using PKUDDS.