Quorum sensing mechanisms have been studied in prokaryotic and eukaryotic microorganisms and play a key role in the behavior of microbial populations within a community. After the development of the next generation sequencing technologies, a great abundance of genomic and metagenomic sequences have been made available in the databases, and together with the advances in bioinformatic tools to study these sequences, have expanded the potential for the in silico study of QS genes and proteins in different organisms and in different habitats. The in silico screening of genomes and metagenomes present advantages and disadvantages compared with the classical genomic and metagenomic studies, allowing the screening of a massive amount of information. These techniques open a window to new ecological and evolutionary studies, as well as to the discovery of new QS genes and proteins with clinical and biotechnological potential.