Aggregation-induced emission (AIE) photosensitizers are a groundbreaking innovation in antimicrobial photodynamic inactivation (aPDI), offering a solution to the limitations of traditional photosensitizers that suffer from aggregation-caused quenching (ACQ). AIE photosensitizers exhibit enhanced luminescence upon aggregation, enabling efficient reactive oxygen species (ROS) generation, photostability, and robust performance in aqueous and biological environments. These properties make them highly effective for targeting and inactivating a broad spectrum of microbial pathogens, including multidrug-resistant bacteria, fungi, and biofilms. This chapter provides a detailed overview of the design principles and mechanisms underlying AIE photosensitizers, with a focus on their photophysical characteristics and the pathways of ROS-mediated microbial destruction. It discusses innovative molecular engineering strategies, including conjugation with targeting moieties and the development of nanostructured AIE systems, to enhance antimicrobial specificity and therapeutic outcomes. Recent advancements and case studies are highlighted, demonstrating their application in diverse fields such as clinical therapeutics, food safety, and environmental disinfection.