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Microorganisms represent the majority of life on earth, populating a wide range of niches on its surface, underground, in the oceans, in the atmosphere, and both on and inside all multicellular organisms. This “microbiome” will clearly play a critical role as humans struggle to deal with society's major challenges—health care, agriculture, energy, and the environment. As one example, the human gut microbiome contributes 36% of the small molecules that are found in human blood, and it also plays a major role in creating susceptibility to certain human diseases. In recent years, a variety of microbial communities have been characterized through such efforts as the Human Microbiome Project and the Earth Microbiome Project. But mapping these trillions upon trillions of microbes and analyzing the vast amounts of data that are accumulating will require new integrative approaches aimed at understanding how microorganisms function and are interrelated.