The goal of this work is to demonstrate the utility of using systematically formatted mixture based libraries as part of the drug discovery processes. While there are a number of different valid approaches for identifying hit and tool compounds, systematically formatted mixture based libraries, such as those described in this study, offer the ability to develop a significant amount of structure activity relationship data from the testing of very few samples. In support of this claim a review of recent developments in the area of systematically formatted mixture based libraries as well as three case studies are presented. The three case studies provide the detailed approach and results obtained from using systematically formatted mixture based libraries in programs focused on identifying broad spectrum antibiotics, therapeutics to treat leishmaniasis, and inhibitors of palmitoylation. In each of these three cases approximately 200 samples were utilized to survey millions of compounds in order to develop a series of hit and tool compounds as well as significant structure-activity relationship (SAR) data around the compounds identified. This information will be utilized in future studies to potentially uncover novel mechanisms of action for treating infections and diseases as well as developing therapeutics to treat the patients affect by them. So while systematically formatted mixture based libraries are not the only option for identifying hit or tool compounds they do provide a very efficient method that can be adapted to a variety of assay formats and therefor should be considered when conducting a screening campaign.