The Human Microbiome Project (HMP) is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the ‘‘other genome’’ of microbes carried in and on the human body. Microbial ecologists, realizing that .99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ, primarily by sequencing the 16S ribosomal RNA gene(16S)asaphylogenetic and taxonomic marker to identify members of microbial communities. The need to develop corresponding new methods for culture-independent studies in turn precipitated a sea change in the study of microbes and human health, inspiring the new term ‘‘metagenomics’’ both to describe a technological approach — sequencing and analysis of the genes from whole communities rather than from individual genomes — and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions culminated in a National Academy of Science report, which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.