Ten years ago next-generation sequencing (NGS) technologies appeared on the market. During the past decade, tremendous progress has been made in terms of speed, read length, and throughput, along with a sharp reduction in per-base cost. Together, these advances democratized NGS and paved the way for the development of a large number of novel NGS applications in basic science as well as in translational research areas such as clinical diagnostics, agrigenomics, and forensic science. Here the authors provide an overview of the evolution of NGS and discuss the most significant improvements in sequencing technologies and library preparation protocols. They also explore the current landscape of NGS applications and provide a perspective for future developments.