One of the key interests in the recent development of fluorescent molecular sensors and switches is the realization of systems that show strong signal changes as a response to the chemical trigger. Aiming at rational probe design, this article compiles and compares different promising strategies to extract those supramolecular and photophysical features that allow the construction of molecular devices suitable for efficient signaling. The examples comprise fluorescence ‘OFF’–‘ON’ as well as ‘ON’–‘OFF’ operative systems and the mechanisms, properties, and limitations of the different design concepts are discussed.