Bacillus amyloliquefaciens FZB42 is a Gram-positive, plant-associated bacterium, which stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. Its 3918-kb genome, containing an estimated 3693 protein-coding sequences, lacks extended phage insertions, which occur ubiquitously in the closely related but nonplant-associated Bacillus subtilis 168 genome. The B. amyloliquefaciens FZB42 genome reveals an unexpected potential to produce secondary metabolites. More than 8.5% of the genome is devoted to synthesizing antibiotics and siderophores by pathways not involving ribosomes. Besides five-gene clusters, known for B. subtilis to mediate the nonribosomal synthesis of secondary metabolites, four giant gene clusters absent in B. subtilis 168 were identified. Examples are the antibacterial polyketides macrolactin and difficidin and the antifungal lipopeptide bacillomycin D. We have demonstrated that FZB42 represents a group of closely related B. amyloliquefaciens strains, which are able to colonize plant roots. They are distinguished by several physiological and genomic features from the B. amyloliquefaciens strains, known as the producer of industrial important enzymes, and designated presently as B. amyloliquefaciens subsp. amyloliquefaciens. B. amyloliquefaciens FZB42T has been recognized as type strain for the “plantarum” subspecies and was subject of intensive research throughout the last 10 years. In total, 13 gene clusters were found, which are involved in nonribosomal and ribosomal synthesis of polyketides and peptides (lipopeptides and bacteriocins) with antagonistic action against numerous microorganisms competing with FZB42T at the plant root surface. Most of them are parts of the core genome shared with other representatives of the B. amyloliquefaciens subsp. “plantarum”. However, the gene clusters devoted to conventional synthesis of the bacteriocins, mersacidin, and plantazolicin are located within genomic islands, which were presumably acquired by events of horizontal gene transfer.