Each human body hosts, on the surface and inside its body, trillions of microorganisms, which are essential in the functioning of the human organisms. The importance of these communities of microorganisms in our lives is major since researchers all over the world consider them a "second human genome". Understanding how these organisms interact with their human hosts could explain different aspects of many complex diseases, from obesity and metabolic diseases to infections susceptibility or the occurrence of several chronic diseases (neurological, cardiovascular), immunological and autoimmune diseases, or even behavioral changes (depression, anxiety), autism and the ADHD (Attention Deficit Hyperactivity Disorders) in children. In this short review are presented the main challenges and recent discoveries in biotechnological approaches worldwide applied, especially within Human Microbiome Project.