• Impressive advances in NGS have enabled an immense diversity of novel applications. • The barrier of the $1000 genome has recently been broken. • Important novel tools for clinical diagnostics based on NGS are appearing. • Third-generation technologies may further revolutionize genomics research. • Significant challenges for NGS remain, in particular data storage and processing. 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 we provide an overview of the evolution of NGS and discuss the most significant improvements in sequencing technologies and library preparation protocols. We also explore the current landscape of NGS applications and provide a perspective for future developments.