Microorganisms, majorly bacteria, are meticulously involved in causing a wide range of clinical manifestations. Antibiotics are agents that control or inhibit the targeted microbial growth but with the course of evolution, bacteria have evolved resistance against common antimicrobial agents, hence development of new agents is crucial in the foreseeable future. This chapter will provide information on antibacterial agents, their discovery, classification based on varying sources, functions, spectrum of activity, and chemical structures with special reference to Polyhydroxyalkanoates (PHAs) as antibacterial agents. Further, various approaches can be implied for developing novel antibacterial agents by either modifying known drug molecules, inhibiting resistance mechanism, a new molecule with a novel mechanism, or a combination that can restore the drug’s prior effect. The major challenges include the lack of innovative assays for hit discovery, optimisation, extensive expenditure, and broad timelines. The development of novel antibacterial drugs in combating resistance can be improved by exploiting the emerging artificial intelligence-based technologies, regulating host response pathways, and employing a combination of distinct antibiotics/PHAs/Plant-derived compounds/Engineered pro-drugs.