Surgical resection is currently the most common and effective strategy for clinical diagnosis and treatment of diseases; especially fluorescence navigation can greatly improve the accuracy of surgeons to determine the location of the lesion. Conventional fluorescent probes will reduce sensitivity and accuracy due to aggregation-caused quenching effect. In view of this, this entry focuses on the development of new AIEgen-based fluorescence probes for fluorescence navigation imaging in a variety of common diseases, especially the application of NIR probes with high fluorescence quantum yields and deep tissue penetration in this field. This section aims to inspire new insights on the development of advanced fluorescent navigation techniques based on novel AIEgens for future clinical studies.