It is often impractical to synthesize and test all compounds in a large exhaustive chemical library. Herein, we discuss rational approaches to selecting representative subsets of virtual libraries that help direct experimental synthetic efforts for diverse library design. We compare the performance of two stochastic sampling algorithms, Simulating Annealing Guided Evaluation (SAGE; Zheng, W.; Cho, S. J.; Waller, C. L.; Tropsha, A. J. Chem. Inf. Comput. Sci. 1999, 39, 738-746.) and Stochastic Cluster Analysis (SCA; Reynolds, C. H.; Druker, R.; Pfahler, L. B. Lead Discovery Using Stochastic Cluster Analysis (SCA): A New Method for Clustering Structurally Similar Compounds J. Chem. Inf. Comput. Sci. 1998, 38, 305-312.) for their ability to select both diverse and representative subsets of the entire chemical library space. The SAGE and SCA algorithms were compared using u- and s-optimal metrics as an independent assessment of diversity and coverage. This comparison showed that both algorithms were capable of generating sublibraries in descriptor space that are diverse and give reasonable coverage (i.e. are representative) of the original full library. Tests were carried out using simulated two-dimensional data sets and a 27 000 compound proprietary structural library as represented by computed Molconn-Z descriptors. One of the key observations from this work is that the algorithmically simple SCA method is capable of selecting subsets that are comparable to the more computationally intensive SAGE method.