Deciphering the complex mechanisms controlling cells and organisms requires effective imaging systems and fluorescent probes to observe and quantify biomolecules in real time with high spatiotemporal resolution. A common strategy for imaging proteins is to fuse them to peptide or protein sequences that provide fluorescence (e.g. fluorescent proteins). Recently, the fluorescence toolkit has been expanded with methods for labeling biomolecules with exogenously applied small synthetic fluorescent probes. These innovative technologies offer additional labeling refinement and broaden fluorescent labeling to more diverse cellular molecules. Selectivity is ensured through fusion to a genetic tag that binds selectively tailored fluorescent molecules. The modular nature of such an approach enables to tune the synthetic part by molecular engineering, in order to address biological questions with the molecular diversity offered by modern chemistry. To be usable within living systems, the genetic tag must fold and function in various cellular compartments, while the fluorescent probes must ideally not show unspecific interaction/reaction with cell components. A way to avoid unspecific background in cells and achieve high imaging contrast is to use fluorescent probes that display no fluorescence until labeling occurs. Such probes are often called fluorogenic probes to highlight their ability to generate fluorescence upon reaction/interaction with their target. During this talk, I will present the development and applications of tunable fluorescent markers that enable high imaging contrast relying on genetically encoded protein that bind and activate fluorogenic synthetic molecules.