Fluorescent sensing has emerged as a powerful tool for detecting various analytes and visualizing numerous biological processes by virtue of its superb sensitivity, rapidness, excellent temporal resolution, easy operation, and low cost. Of particular interest is activity-based sensing (ABS), a burgeoning sensing approach that is actualized on the basis of dynamic molecular reactivity rather than conventional lock-and-key molecular recognition. ABS has been recognized to possess some distinct advantages, such as high specificity, extraordinary sensitivity, and accurate signal outputs. A majority of ABS sensors are constructed by modifying conventional fluorogens, which are strongly emissive when molecularly dissolved in solvents but experience emission quenching upon aggregate formation or concentration increase. The aggregation-caused quenching (ACQ) phenomenon leads to a limited amount of labeling of the analyte with the sensor and low photobleaching resistance, which could impede practical applications of the ABS protocol. As an anti-ACQ phenomenon, aggregation-induced emission (AIE) provides a straightforward solution to the ACQ problem. Thanks to their intrinsic advantages, including high photobleaching threshold, high signal-to-noise ratio, fluorescence turn-on nature, and large Stokes shift, AIE-active luminogens (AIEgens) represent a class of extraordinary fluorogen alternatives for the ABS protocol. The use of AIEgen-involved ABS can integrate the advantages of AIEgens and ABS, and additionally, the AIE process offers some unique properties to the ABS approach. For instance, in some cases of water-soluble AIEgen-involved ABS, chemical reaction not only leads to a chang in the emission color of the AIEgens but also causes solubility variations, which could result in specific "light-up" signaling. In this Account, the basic concepts and mechanistic insights of the ABS approach involving the AIE principle are briefly summarized, and then we highlight the new breakthroughs, seminal studies, and trends in the area that have been most recently reported by our group. This emerging sensing protocol has been successfully utilized for detecting an array of targets including ions, small molecules, biomacromolecules, and microenvironments, all of which closely relate to human health, medical, and public concerns. These detections are smoothly achieved on the basis of various reactions (e.g., hydrolysis, boronate cleavage, dephosphorylation, addition, cyclization, and rearrangement reactions) through different sensing principles. In these studies, the AIEgen-involved ABS strategy generally shows good biocompatibility, high selectivity, excellent reliability and high signal contrast, strongly indicating its great potential for high-tech innovations in the sensing field, among which bioprobing is of particular interest. With this Account, we hope to spark new ideas and inspire new endeavors in this emerging research area, further promoting state-of-the-art developments in the field of sensing.