Recent discoveries and applications involving small-molecule microarrays

•We review selected recent probe discoveries and novel applications using SMMs.•SMM screening can use purified protein and proteins from cellular lysates.•Both strategies have yielded effective probes and inhibitors for a wide variety of targets.•SMMs enable functional proteomics-biomarker discovery and reactivity profiling. High-throughput and unbiased binding assays have proven useful in probe discovery for a myriad of biomolecules, including targets of unknown structure or function and historically challenging target classes. Over the past decade, a number of novel formats for executing large-scale binding assays have been developed and used successfully in probe discovery campaigns. Here we review the use of one such format, the small-molecule microarray (SMM), as a tool for discovering protein–small molecule interactions. This review will briefly highlight selected recent probe discoveries using SMMs as well as novel uses of SMMs in profiling applications.