Abstract: The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases encoded by NTRK genes play an important role in the development and normal functioning of the nervous system. NTRK fusions are oncogenic drivers of various adult and pediatric cancers. Therefore, TRKs inhibitors have attracted extensive attention with intensive investigation in the past decade. The successful approval of the first-generation TRK inhibitors, larotrectinib and entrectinib, was of monumental significance. As with other tyrosine-kinase inhibitors, resistance can develop over time in patients receiving TRK inhibitors. Therefore, solving drug resistance and multiple mutations will be the focus of future research & development. This review summarizes the recent reports and development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity to provide reference for the further development of novel TRK inhibitors.