Formaldehyde (FA) as a double-edged sword is incisively and vividly exhibited in our life. The occurrence and progression of many diseases is demonstrated to be relavent to FA. Furthermore, as a component of indoor air pollution, it has already caused great troubles to us but little high-efficiency methods to detect. Notably, fluorescent probe has many advantages in detecting and real-time sensing/imaging FA. In current review, we first systematically introduce the exogenous and endogenous FA produced in living systems, along with the biological level of FA. Subsequently, related diseases caused by FA are detailed highlighted. Finally, we make a generalization and summarization of the reaction-based fluorescent detection of FA on the ground of different reaction mechanisms. The emphasis of this review is not just a sumarry of developing fluorescent FA probes, but also driving the participation to deeply explore the relationship between FA and pathological and physiological processes with fluorescent tools.