Microbes represent the most diverse and most abundant group of living organisms. Our knowledge about the biology of prokaryotic microorganisms is mainly obtained from a small minority of lab-cultivable species. Whole-genome sequencing during the last 20 years has pushed this field substantially, and has helped to establish molecular models of microbial lifestyles in even extreme habitats. Applications of this research include fundamental topics such as human health and nutrition, climate change and sustainable use of global resources. Novel technologies, such as metagenomics and single-cell genomics, are currently extending the scope of genomics towards the majority of uncultivable species. These methods rely on sophisticated computational approaches for assembly, binning and annotation of microbial genomes. This talk will give an overview on the latest developments in this field and will discuss remaining challenges. It will further address the implications of the quickly growing number of automatically assembled, near-complete genomes for genome databases, comparative genomics and systems biology of microbes.