Eukaryotic organisms co-evolved with microbes from the environment forming holobiotic meta-genomic units. Members of host-associated microbiomes have commensalic, benefical / symbiotic or pathogenic phenotypes. More than 100 years ago, Lorenz Hiltner, pioneer of soil microbiology, introduced the term "Rhizosphere" to characterize the observation that a high density of saprophytic, beneficial and pathogenic microbes are attracted by root exudates. The balance between these types of microbes decide about the health of the host. Nowadays we know, that for the interaction of microbes with all eukaryotic hosts similar principles and processes of cooperative and competitive functions are in action. Small diffusible molecules like (phyto)hormones, volatiles and quorum sensing signals are examples for mediators of interspecies and cross-kingdom interactions. Quorum sensing (QS) of bacteria is mediated by different auto-inducible metabolites in a density dependent manner. In this perspective publication, the role of QS-related activities for the health of hosts will be discussed focussing mostly on N-acyl-homoserine lactones (AHL). It is also considered that in some cases very close phylogenetic relations exist between plant beneficial and opportunistic human pathogenic bacteria. Based on a genome and system-targeted new understanding, sociomicrobiological solutions are possible for the biocontrol of diseases and the health improvement of eukaryotic hosts.