Antibiotic resistance is one of the world's most urgent public health problems. Antimicrobial photodynamic therapy (aPDT) is a promising therapy to combat the growing threat of antibiotic resistance. The aPDT combines a photosensitizer and light to generate reactive oxygen species to induce bacterial inactivation. Ruthenium polypyridyl complexes are significant because they possess unique photophysical properties that allow them to produce reactive oxygen species upon photoirradiation, which leads to cytotoxicity. These antimicrobial agents cause bacterial cell death by DNA and cytoplasmic membrane damage. This article presents a comprehensive review of photoactive antimicrobial properties of kinetically inert and labile ruthenium complexes, nanoparticles coupled photoactive ruthenium complexes, and photoactive ruthenium nanoparticles. Additionally, limitations of current ruthenium‐based photoactive antimicrobial agents and future directions for the development of antibiotic‐resistant photoactive antimicrobial agents are discussed. It is important to raise awareness for the ruthenium‐based aPDT agents in order to develop a new class of photoactive metalloantibiotics capable of combating antibiotic resistance.