Systems biology promises to describe and model complete biological systems quantitatively. Recently, in many areas of biological research, focus has shifted from detailed characterization of an individual gene or gene function in terms of its effect on a cellular process (the reductionist approach) to understanding the behavior of networks of genes or gene products from a genome-wide perspective (the systems biology approach). Here we review how analyses that allowed genome-wide investigations (by mining and integrating data from various “omics”) have contributed to our understanding of biological processes from genes to networks. We will discuss these advances in terms of quantitative leaps in which the scope of a known process was only revealed by genome studies (e.g., fraction of genes with alternative transcription start sites, splicing isoforms, or protein isoforms) and qualitative leaps in which completely new phenomena have been revealed (e.g., dark matter in the genome, functional pseudogenes, scale-free protein networks, fluidity of microbial genomes, and the diversity of the microbiome). We will discuss what the future holds for systems biology in terms of unrealized leaps that may provide new surprises from the viewpoints of academic and biomedical research.