Metagenomics, also referred to as environmental or community genomics, has brought about radical changes in the ability to analyze complex microbial communities by direct sampling of their natural habitat. Metagenomics has truly revolutionized biology and medicine, and changed the way in which genomics is studied. To date, many metagenomic studies have been undertaken, with samples from diverse habitats including the oceans, soil, air, human, and animal hosts having been subject to metagenomic examinations. Currently, huge national and international projects, aimed at elucidating the biogeography of microbial communities living within and on the human body, are well underway. The analysis of human microbiome data has brought about a paradigm shift in the present understanding of the role of resident microorganisms in human health and disease, and brings nontraditional areas such as gut ecology to the forefront of personalized medicine. In parallel, rapid technological advances in DNA sequencing methods have reduced the time and costs associated with sequencing while at the same time significantly increasing the data output. As genome sequencing becomes cheaper, it is being applied to sequence complex metagenomes, and large-scale 16S ribosomal DNA sequencing has become far more routine. Today, metagenomics is proving to be a powerful tool, considerably enhancing the present understanding of the extent and role of microbial diversity in their natural habitats, and in many ecologically important environments, with far greater implications on human health and disease. An overview of the current literature, together with details of projects and the state-of-the-art in microbiome studies, are presented in this chapter.