Sanger and his colleagues invented the DNA sequencing technology by cleverly applying the function of DNA polymerase to DNA sequence detection in 1977. Human Genome Project (HGP) launched in the early 1990s greatly facilitated the progress of the DNA sequencing technology and prompted the automation of DNA sequencing which conversely accelerate the human genome draft accomplished in 2001. For the past decade, great advancements in the speed and sequencing throughput in the next generation sequencing (NGS) technologies have dramatically reduced the cost of the whole genome sequencing to $1000. Although there is no great improvement in technique for NGS compared with the first generation sequencing in the basic principle of sequencing, the second generation sequencing system processes the quantified sequencing fragments in massive parallel way, which makes sequencing throughput increased significantly and at the same time greatly reduce the cost. Recently, the third generation sequencing technologies emerge with the advantages of very long sequencing fragment and no need for PCR amplification during the sequencing process, which significantly decrease the complex of assembling process and avoid the potential bias and false variations caused by PCR technology. Although the accuracy of the third generation sequencing technologies can only reach about 85% and the price is relatively high, the technologies still show their promising future with the gradual improvement in experiment processes and computational methods. When biomedical researches and clinical applications will benefit from the technology innovation, the enormous applications of NGS in precision medicine and biomedical research fields will further accelerate the progress and innovations in NGS. At the same time, with the vast accumulation of massive sequencing data, how to efficiently analyze and interpret those data becomes a big challenge, bioinformatics plays the key role in the process. Well trained bioinformaticians with good background of mathematics, statistics, computer skills and biology are in high demand. It can be anticipated that the continuous innovations in NGS technology will further significantly decrease the cost for the human genome sequencing and promise the advent of the era with the sequencing cost close to $100, which will push personal genome sequencing widely used in clinical applications and make the precision medicine come true in daily life.