Phage therapy, the use of bacteriophages to treat bacterial infections, is regaining attention as a promising alternative to combat multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, modern resurgence, and advancements in phage therapy, including its mechanisms of action and applications. Phages are highly specific to their bacterial hosts, minimizing collateral damage and reducing the risk of resistance. They are effective against biofilm-associated infections and intracellular pathogens, and their use is expanding into vaccine development, cancer therapy, and gene delivery systems. Despite its potential, phage therapy faces challenges such as phage stability, immune response, and regulatory approval. The review highlights the need for ongoing research and technological advancements to overcome these hurdles and integrate phage-based therapies into modern medical practices. Key mechanisms of phage action, including adsorption, genome injection, replication, and host takeover, are discussed, along with the benefits of engineered phages and their combination with antibiotics. The review also examines phage therapy's effectiveness against MDR bacteria, biofilm-forming bacteria, and intracellular pathogens, supported by clinical studies and case reports. Finally, it addresses regulatory and safety considerations, emphasizing the importance of standardized protocols and rigorous clinical trials for phage therapy.Phage therapy, the use of bacteriophages to treat bacterial infections, is regaining attention as a promising alternative to combat multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, modern resurgence, and advancements in phage therapy, including its mechanisms of action and applications. Phages are highly specific to their bacterial hosts, minimizing collateral damage and reducing the risk of resistance. They are effective against biofilm-associated infections and intracellular pathogens, and their use is expanding into vaccine development, cancer therapy, and gene delivery systems. Despite its potential, phage therapy faces challenges such as phage stability, immune response, and regulatory approval. The review highlights the need for ongoing research and technological advancements to overcome these hurdles and integrate phage-based therapies into modern medical practices. Key mechanisms of phage action, including adsorption, genome injection, replication, and host takeover, are discussed, along with the benefits of engineered phages and their combination with antibiotics. The review also examines phage therapy's effectiveness against MDR bacteria, biofilm-forming bacteria, and intracellular pathogens, supported by clinical studies and case reports. Finally, it addresses regulatory and safety considerations, emphasizing the importance of standardized protocols and rigorous clinical trials for phage therapy.