The ability of cells and tissues to degrade proteins in a selective manner is critical for virtually every important cellular function, from cell division to tissues development. Moreover, impaired protein homeostasis is intrinsically linked to many types of diseases. To overcome major obstacles in the functional investigation of protein homeostasis in the living organism we have developed fluorescent timer proteins that enable the direct visualization of protein turnover in vivo, and also permit mapping of cellular protein turnover pathways and determinants based on high throughput approaches.