The scaffold diversity of 7 representative commercial and proprietary compound libraries is explored for the first time using both Murcko frameworks and Scaffold Trees. We show that Level 1 of the Scaffold Tree is useful for the characterization of scaffold diversity in compound libraries and offers advantages over the use of Murcko frameworks. This analysis also demonstrates that the majority of compounds in the libraries we analyzed contain only a small number of well represented scaffolds and that a high percentage of singleton scaffolds represent the remaining compounds. We use Tree Maps to clearly visualize the scaffold space of representative compound libraries, for example, to display highly populated scaffolds and clusters of structurally similar scaffolds. This study further highlights the need for diversification of compound libraries used in hit discovery by focusing library enrichment on the synthesis of compounds with novel or underrepresented scaffolds.