Long-read sequencing (LRS) methods can now produce highly accurate (ultra)long reads and thus enable for the first time the production of truly complete telomere-to-telomere (T2T) assemblies of complex genomes.While the recently produced T2T assemblies were labor-intensive and required a combination of various techniques, in the near future T2T assemblies based on LRS alone will be produced.We have entered the era of population scale long-read sequencing, where graph-based pangenomes much better representing genomic variation will increasingly be used in the near future.New applications of LRS appear at a rapid pace, with examples ranging from higher order chromatin interaction studies to the quality control of mRNA vaccines. Long-read sequencing (LRS) technologies have provided extremely powerful tools to explore genomes. While in the early years these methods suffered technical limitations, they have recently made significant progress in terms of read length, throughput, and accuracy and bioinformatics tools have strongly improved. Here, we aim to review the current status of LRS technologies, the development of novel methods, and the impact on genomics research. We will explore the most impactful recent findings made possible by these technologies focusing on high-resolution sequencing of genomes and transcriptomes and the direct detection of DNA and RNA modifications. We will also discuss how LRS methods promise a more comprehensive understanding of human genetic variation, transcriptomics, and epigenetics for the coming years.