Microbial secondary metabolites have been a major source for drug discovery and development due to their structural novelty and diversity. Microbial secondary metabolites, typically encoded by specific biosynthetic gene cluster(BGC), are non-essential for the growth and propagation of the microbes. Despite the abundant existence of microbes, the majority of them are unculturable under laboratory conditions. Moreover, given that most of the BGCs from culturable microbes are silent, the discovery of novel microbial secondary metabolites has been hampered. Recently, the heterologous expression of BGCs has become an attractive approach to discover various microbial secondary metabolites, among which TAR-based heterologous expression is one of the important tools. This review summarized the principle of TAR, the applications and the advanced strategies of TAR-based methods for heterologous expression of secondary metabolites, which may help the advancements of drug discovery and development from microbial sources.