The human gut contains microbial populations whose role in health and disease has recently been underscored by researchers. This chapter aims to highlight the function, diversity, and changes in the human microbiome that relate to health and disease. The human microbiome as a key player in health is multifaceted and changes throughout the human lifespan. The role of diet, especially the Mediterranean diet, will be discussed. The manipulation of the gut microbiome to minimize or eliminate dysbiosis will also be addressed. Finally, an individual’s health status can be seen as an expression of their microbiome, and personalized nutrition should be based on this parameter.