Fluorescent dyes have been used for bioimaging for long time, but the conventional wisdom says the organic dyes are sticky and leave high background in the biological system. Prof. Chang and collaborators dreamed no-background imaging probes and challenged to figure the physico-chemical properties of such ideal dyes. By testing fluorescent library combined with chemoinformatic analysis, they found three main parameters to achieve the holy grail. The process they called “taming” and the tamed dyes will be of general use for future bioimaging.