Abstract: Abnormal accumulation of Tau protein, the primary indicator of Alzheimer(AD) and non-AD Tau-protein diseases, is closely associated with neurodegeneration and cognitive impairment. In recent years, several first-generation specific Tau-protein PET molecular probes, including ¹⁸F-THK5351, ¹⁸F-AV1451, and ¹¹C-PBB3, have been developed and tested in clinical trials. Off-target binding is commonly used in first-generation PET molecular probes to promote the development of second-generation specific Tau-protein PET molecular probes with high binding affinity and selectivity. The potential of Tau-protein PET imaging as a biomarker in tauopathies and the latest progress in novel Tau molecular probes is reviewed in this study.