Lately, the study of symbiotic interactions between a eukaryotic host and its microbiota, i.e., a holobiont, has become a primary topic of biological science. It turns out that such interactions are essential for human physical and mental wellbeing, as well as for evolution as such. The term holobiont usually denotes a ‘whole ’ living entity, which involves not only a host but also all its symbionts. The chapter concerning the holobiotic interactions begins with the division of the term holobiont and superoganism. The chapter mainly discusses the human gut conditions because it is the most frequently studied holobiotic niche, especially the microbiome variation within individuals and its possible causes, the colonization determinants, and the colonization of the newborn as such. The functions of the microbiome in human health and development and its possible links to various diseases are also discussed. The chapter closes with the current discussion on holobiotic theory, including the holobiont as a unit of selection.