Antimicrobial resistance (AMR) is a growing global health crisis that demands innovative, non-antibiotic treatment strategies. The chapter explores how femtosecond laser technology achieves revolutionary antimicrobial photoinactivation of drug-resistant pathogens. Femtosecond lasers operate without external photosensitizers to kill bacteria by producing high-intensity ultrashort pulses, which initiate photothermal and photomechanical, and photochemical reactions. The combination of protein denaturation and membrane disruption alongside shockwave generation and reactive oxygen species (ROS) production enables effective bacterial cell destruction. This chapter assesses the fundamental processes that femtosecond lasers use to kill microbes by explaining their effects on natural chromophores, including porphyrins and flavins. The chapter surveys essential research that proves that light wavelength determines the effectiveness of bacterial destruction against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), Pseudomonas aeruginosa, and Escherichia coli. Bactericidal effectiveness peaks when researchers optimize laser wavelength along with exposure time and energy density to protect surrounding tissues from damage. Also, this chapter reviews recent technological progress that merges femtosecond lasers with medical devices through fiber-optic delivery systems and clinical implementation. Initial clinical research indicates encouraging outcomes for managing infected wounds, which establishes a basis for extensive therapeutic use. Femtosecond lasers combine precise and non-invasive methods with high effectiveness to defeat antimicrobial resistance, thus making them a future antimicrobial device with significant medical prospects.