Nowadays, the increasing emergence of antibiotic-resistant pathogenic microorganisms requires the search for alternative methods that do not cause drug resistance. Phototherapy strategies (PTs) based on the photoresponsive materials have become a new trend in the inactivation of pathogenic microorganisms due to their spatiotemporal controllability and negligible side effects. Among those phototherapy strategies, photocatalytic antimicrobial therapy (PCAT) has emerged as an effective and promising antimicrobial strategy in recent years. In the process of photocatalytic treatment, photocatalytic materials are excited by different wavelengths of lights to produce reactive oxygen species (ROS) or other toxic species for the killing of various pathogenic microbes, such as bacteria, viruses, fungi, parasites, and algae. Therefore, this review timely summarizes the latest progress in the PCAT field, with emphasis on the development of various photocatalytic antimicrobials (PCAMs), the underlying antimicrobial mechanisms, the design strategies, and the multiple practical antimicrobial applications in local infections therapy, personal protective equipment, water purification, antimicrobial coatings, wound dressings, food safety, antibacterial textiles, and air purification. Meanwhile, we also present the challenges and perspectives of widespread practical implementation of PCAT as antimicrobial therapeutics. We hope that as a result of this review, PCAT will flourish and become an effective weapon against pathogenic microorganisms and antibiotic resistance.