Phage therapy, using bacteriophages to target and destroy bacteria, has evolved significantly from its early 20th-century inception to its modern resurgence as a promising alternative to antibiotics. This review explores the historical development of phage therapy, detailing its initial successes, subsequent decline with the rise of antibiotics, and recent revival in response to increasing antibiotic resistance. We examine the fundamental mechanisms of phage therapy, including the specificity of phages for bacterial targets and their ability to combat resistant strains. Current applications are discussed, highlighting the use of phage therapy in treating chronic infections, personalizing treatment strategies, and its role in veterinary and food safety contexts. Innovations in phage therapy, driven by advancements in genetic engineering and synthetic biology, are also reviewed, showcasing the development of engineered phages, phage libraries, and novel delivery systems. Despite its potential, phage therapy faces challenges such as regulatory hurdles, safety concerns, and issues related to bacterial resistance to phages. The review underscores the need for ongoing research and clinical trials to address these challenges and to integrate phage therapy into modern treatment paradigms. By offering a detailed overview of the evolution, current status, and future directions of phage therapy, this review aims to highlight its potential as a crucial component in the fight against antibiotic-resistant infections and to inform future research efforts.