Completion of the Human Genome Project has been rapidly followed by the emergence of high-throughput technologies that combine automation, miniaturization, and many other strategies and tools to enable systematic surveys of genome composition and gene expression. Of particular relevance to the prevention and management of disease are technologies such as high-throughput DNA genotyping, microarray-based gene-expression profiling, and mass spectrometry-facilitated protein profiling--platforms that collectively support the comprehensive analysis of DNA sequence variants across the genome and the global gene and protein expression changes that distinguish health from disease. Now used extensively in all facets of biomedical investigation, genomic and proteomic tools are already beginning to pinpoint molecular variants that influence risk and outcome in common diseases, and to thereby inform and direct development of novel molecular biomarkers and drug targets. As evidenced by recent advances in DNA sequencing methods, continued improvements in the scope, power, and cost efficiency of genomic and proteomic technologies should ensure their capacity to provide the scale and depth of knowledge required for translating genome sequence information into major medical impact.