The most prevalent biological species in the biosphere are microbes. Due to the limits of current culturing technologies, it is difficult to identify and quantify microorganisms in the biosphere, including viruses, bacteria, fungi, and protists. Through the development of a nonculture-based method known as “metagenomics,” researchers were able to thoroughly study microbial populations across many habitats. To summarize, we present an overview of the latest developments in the metagenomics technique for examining alterations in microbial populations. Using high-throughput sequencing data to decipher the taxonomic makeup and functional potential of microbial communities using USEARCH, a flexible bioinformatics tool. A thorough understanding of community dynamics is made possible by the accurate identification of microorganisms made possible by the incorporation of USEARCH in metagenomic workflows. This abstract highlights the importance of USEARCH in expanding our understanding of microbial ecology by summarizing the approach and major discoveries made possible by its application.