Gradients of physicochemical factors influence the growth and survival of life in deep-sea environments. Insights into the characteristics of deep marine prokaryotes has greatly benefited from recent progress in whole genome and metagenome sequence analyses. Here we review the current state-of-the-art of deep-sea microbial genomics. Ongoing and future genome-enabled studies will allow for a better understanding of deep-sea evolution, physiology, biochemistry, community structure and nutrient cycling.