The availability of genome sequences from a multitude of organisms, which began about a decade ago, has had enormous impact throughout the biomedical sciences. These sequence data have changed the way research studies are carried out and have led to the explosive growth of computational biology as an approach to analyze biological processes and evolution. In medicine, the completion of the human genome sequence has illuminated the function of many genes, facilitated the correlation of mutant genes to disease phenotypes, and provided a basis for the study of human variation. At the University of Washington, the two academic departments whose overall programs were most centrally affected by the sequencing revolution were Genetics and Molecular Biotechnology. These departments were fused in 2001 to form the Department of Genome Sciences in order to best exploit these developments and to become a prototype for the basic biomedical science department of the future. The department's goal is to address leading-edge questions in biology and medicine through the application of genetics, genomics, proteomics, and computational approaches to the increasing collection of known genome sequences and their encoded products. The authors review the events that led up to the founding of this department and discuss the initiatives that have been undertaken, which include the recruitment of faculty, the establishment of a new interdisciplinary graduate program, the continued development of an outreach program, and the construction of a building to house the department. Lessons learned in crafting this department are also discussed, as well as how these might apply to other medical schools.