This review describes recent developments in the evolutionary process of microarrayed compound screening (microARCS to become a robust and efficient ultra-high-throughput screening technology. Improvements in compound spotting (including new quality-control methods), gel casting and imaging, together with software capable of automatic analysis and deconvolution of images, have helped to streamline the screening process. A variety of screening projects using cell-based and non-cell-based approaches have been successfully concluded using microARCS. Comparison of hits derived from standard microtitre-plate-based screening and from microARCS reveals excellent overlap. Furthermore, there seems to be no bias towards finding compounds within a particular range of logP values, even though compounds are solubilized from a dry state during the course of the assay.