It has been 10 years since the invention of differential display (DD), a conceptually simple methodology that allows the detection and identification of differentially expressed genes. In the past decade, the number of publications describing successful applications of DD has outnumbered those using any other competing methodologies, including subtractive hybridization, representational difference analysis, serial analysis of gene expression, and DNA microarrays. This review will provide a glimpse of the current progress made in DD technological development, refinement, and automation. Excellent examples of DD applications in studying a variety of biological problems, in such diverse biological systems as bacteria, yeast, flies, plants, and higher mammals, are presented to provide a roadmap for those who would like to pursue a fruitful gene "fishing" expedition. Some of the fundamental differences between DD and DNA microarrays are also discussed.