The article provides an overview of high-throughput sequencing (HTS) technologies and their applications in genomics. It begins by discussing the historical context of DNA sequencing, highlighting the transition from Sanger sequencing to HTS, which has significantly reduced costs and increased throughput. The article then delves into the details of several commonly used HTS platforms, including Illumina, Ion Torrent, Pacific Biosciences, and Oxford Nanopore Technologies, detailing their sequencing methods, advantages, and limitations. The article also covers a wide range of HTS applications, such as genome sequencing and variation analysis, mapping regulatory information, characterizing the transcriptome, microbiome sequencing, and studying rare diseases and cancer. These applications have provided valuable insights into human diversity, disease genetics, and the molecular mechanisms underlying various conditions. Finally, the article addresses the limitations of current HTS technologies, particularly in terms of accuracy and coverage, and discusses the challenges and future directions for personalized medicine, emphasizing the need for improved data interpretation and integration of multiple sequencing technologies.The article provides an overview of high-throughput sequencing (HTS) technologies and their applications in genomics. It begins by discussing the historical context of DNA sequencing, highlighting the transition from Sanger sequencing to HTS, which has significantly reduced costs and increased throughput. The article then delves into the details of several commonly used HTS platforms, including Illumina, Ion Torrent, Pacific Biosciences, and Oxford Nanopore Technologies, detailing their sequencing methods, advantages, and limitations. The article also covers a wide range of HTS applications, such as genome sequencing and variation analysis, mapping regulatory information, characterizing the transcriptome, microbiome sequencing, and studying rare diseases and cancer. These applications have provided valuable insights into human diversity, disease genetics, and the molecular mechanisms underlying various conditions. Finally, the article addresses the limitations of current HTS technologies, particularly in terms of accuracy and coverage, and discusses the challenges and future directions for personalized medicine, emphasizing the need for improved data interpretation and integration of multiple sequencing technologies.