Targets are one of the most important element in both phenotypic drug discovery and target-based drug discovery.  Over the last decade, quantitative proteomics have become an efficient approach to deciphering action mechanisms and identifying targets of bioactive compounds. In this presentation, I will briefly introduce TMT-based thermal proteome profiling (TPP) and provide examples for identifying targets of different classes of compounds. Quantitative proteomics are also employed to determine the functions of flavonoids at molecular, cellular, tissue, and organism levels. I will also discuss the advantages and challenges of TPP in drug discovery.