Existing approaches to direct genomic studies are costly and time-consuming. To overcome these problems, a series of tag-based methods utilizing short fragments uniquely representing full-length transcripts/genes from which they originate has been developed. This review summarizes basic principles underlying these methods and their numerous modifications designed for studying transcriptome profiles, searching for unidentified expressed loci, characterization of promoter regions, and high-throughput mapping of various genomic sites, such as hypo-and hypermethylated CpGs, and chromatin-binding and DNase I cleavage sites. © 2007 Pleiades Publishing, Ltd.