Threat or treat? While pathogenic bacteria pose significant threats, they also represent a huge reservoir of potential pharmaceuticals to treat various diseases. The alarming antimicrobial resistance crisis and the dwindling clinical pipeline urgently call for the discovery and development of new antibiotics. Pathogenic bacteria have an enormous potential for natural products drug discovery, yet they remained untapped and understudied. Herein, we review the specialised metabolites isolated from entomopathogenic, phytopathogenic, and human pathogenic bacteria with antibacterial and antifungal activities, highlighting those currently in pre-clinical trials or with potential for drug development. Selected unusual biosynthetic pathways, the key roles they play (where known) in various ecological niches are described. We also provide an overview of the mode of action (molecular target), activity, and minimum inhibitory concentration (MIC) towards bacteria and fungi. The exploitation of pathogenic bacteria as a rich source of antimicrobials, combined with the recent advances in genomics and natural products research methodology, could pave the way for a new golden age of antibiotic discovery. This review should serve as a compendium to communities of medicinal chemists, organic chemists, natural product chemists, biochemists, clinical researchers, and many others interested in the subject.