The use of photolabile protecting groups (PPGs) has been growing in emphasis for decades, and nowadays they enable cutting-edge results in numerous fields ranging from organic synthesis to neurosciences. PPGs are chemical entities that can be conjugated to a biomolecule to hide its biological activity, forming a stable so called "caged compound". This conjugate can be simply cleaved by light and therefore, the functionality of the biomolecule is restored with the formation of a PPG by-product. However, there is a sizeable need for PPGs that are able to quantify the "uncaging" process. In this review, we will discuss several strategies leading to an acute quantification of the uncaging events by fluorescence. In particular, we will focus on how molecular engineering of PPG could open new opportunities by providing easy access to photoactivation protocols.