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Plant-beneficial <i>Pseudomonas</i> spp. aggressively colonize the rhizosphere and produce numerous secondary metabolites, such as 2,4-diacetylphloroglucinol (DAPG). DAPG is a phloroglucinol derivative that contributes to disease suppression, thanks to its broad-spectrum antimicrobial activity. A famous example of this biocontrol activity has been previously described in the context of wheat monoculture where a decline in take-all disease (caused by the ascomycete <i>Gaeumannomyces tritici</i>) has been shown to be associated with rhizosphere colonization by DAPG-producing <i>Pseudomonas</i> spp. In this review, we discuss the biosynthesis and regulation of phloroglucinol derivatives in the genus <i>Pseudomonas</i>, as well as investigate the role played by DAPG-producing <i>Pseudomonas</i> spp. in natural soil suppressiveness. We also tackle the mode of action of phloroglucinol derivatives, which can act as antibiotics, signalling molecules and, in some cases, even as pathogenicity factors. Finally, we discuss the genetic and genomic diversity of DAPG-producing <i>Pseudomonas</i> spp. as well as its importance for improving the biocontrol of plant pathogens.