The Human Microbiome Project (HMP) is a multi-institutional, multi-year initiative funded by the National Institutes of Health (NIH) to study the human microbiome. The HMP has established a population-scale framework for metagenomic protocols, generating a comprehensive resource of microbial taxonomic profiles and metagenomic sequences from 242 healthy adults sampled at various body sites. This resource includes over 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and more than 3.5 terabases of metagenomic sequence. The HMP has also sequenced approximately 800 reference strains isolated from the human body. These data provide a critical framework for understanding the composition and function of the human microbiome, and they are available to the scientific community through the Data Analysis and Coordination Center (DACC). The HMP has developed standardized protocols for 16S and metagenomic sequencing, ensuring consistency and accuracy in data production and analysis. The HMP's resources and protocols serve as a model for future studies of the microbiome, enabling informed decisions about sampling protocols, sequencing depth, and statistical power. The HMP's comprehensive catalog of human microbiome data is the largest and most extensive to date, providing a valuable resource for identifying new organisms, gene functions, and metabolic and regulatory networks, as well as correlations between microbial community structure and health and disease.The Human Microbiome Project (HMP) is a multi-institutional, multi-year initiative funded by the National Institutes of Health (NIH) to study the human microbiome. The HMP has established a population-scale framework for metagenomic protocols, generating a comprehensive resource of microbial taxonomic profiles and metagenomic sequences from 242 healthy adults sampled at various body sites. This resource includes over 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and more than 3.5 terabases of metagenomic sequence. The HMP has also sequenced approximately 800 reference strains isolated from the human body. These data provide a critical framework for understanding the composition and function of the human microbiome, and they are available to the scientific community through the Data Analysis and Coordination Center (DACC). The HMP has developed standardized protocols for 16S and metagenomic sequencing, ensuring consistency and accuracy in data production and analysis. The HMP's resources and protocols serve as a model for future studies of the microbiome, enabling informed decisions about sampling protocols, sequencing depth, and statistical power. The HMP's comprehensive catalog of human microbiome data is the largest and most extensive to date, providing a valuable resource for identifying new organisms, gene functions, and metabolic and regulatory networks, as well as correlations between microbial community structure and health and disease.