New technologies that analyze the behavior of thousands of genes in parallel are creating, for the first time, a foundation of data for building integrated models of cellular processes. This review discusses the general issues of utilizing genomic methods in fundamental and applied research settings, using the study of stress responses and improvement of secondary metabolite production as examples. A fusion of concepts from biological and nonbiological disciplines, including mathematics, computer science, physics, chemistry, and engineering, is required to address the theoretical and experimental challenges facing the field of genomics, and together promise great breakthroughs in our understanding and engineering of cellular systems.