Bacteriophage–Host Interactions and the Therapeutic Potential of Bacteriophages Bacteriophages (phages) are promising alternatives to antibiotics in treating bacterial infections due to their specificity. They produce enzymes like endolysins, exolysins, and depolymerases that interact with bacterial surfaces, degrade biofilms, and destroy cell walls. These enzymes help phages adhere to and enter host cells, exposing receptors necessary for infection. Gram-positive bacteria are vulnerable to phage infiltration through peptidoglycan, while Gram-negative bacteria are targeted by lipopolysaccharides and pili. Bacteria defend against phages through physical barriers, CRISPR systems, and other mechanisms. Phage proteins stimulate immune responses and enhance antibiotic susceptibility. This review discusses phage attachment, entry, therapeutic use, and limitations of phage therapy. Phage-derived proteins and genetically engineered phages show potential in treating infections. Phages are classified into families based on morphology, with recent taxonomic changes. They have single-stranded or double-stranded DNA, RNA, or other genetic material. Phage specificity varies, with some infecting multiple strains. Phage-host interactions involve adsorption, entry, and immune evasion. Phages use various strategies to enter host cells, including tail fibers, pili, and exopolysaccharides. Some phages target cell wall structures, while others use plasmid-dependent mechanisms. Phage therapy has shown success in treating antibiotic-resistant infections, but challenges remain, including phage resistance, immune responses, and regulatory issues. Phage therapy has been used to treat multidrug-resistant infections, such as Acinetobacter baumanii and Pseudomonas aeruginosa. Phage cocktails have been effective against Mycobacterium abscessus in cystic fibrosis patients. However, resistance development and immune responses limit phage therapy. Phage-derived proteins, such as lysins and depolymerases, show potential in treating infections by degrading bacterial cell walls and biofilms. These proteins can enhance antibiotic efficacy and reduce biofilm formation. Phage-based therapies are being explored for use in medical devices to prevent biofilm formation. Despite their potential, phage therapy faces challenges, including immune system overstimulation and the risk of phage resistance. Phages are recognized by the immune system, and some studies show no significant immune response. Phage therapy is generally safe but requires further research to optimize its use. Phage-derived proteins and genetically engineered phages offer promising avenues for future treatments. However, more studies are needed to fully understand their therapeutic potential and to address the challenges associated with phage therapy.Bacteriophage–Host Interactions and the Therapeutic Potential of Bacteriophages Bacteriophages (phages) are promising alternatives to antibiotics in treating bacterial infections due to their specificity. They produce enzymes like endolysins, exolysins, and depolymerases that interact with bacterial surfaces, degrade biofilms, and destroy cell walls. These enzymes help phages adhere to and enter host cells, exposing receptors necessary for infection. Gram-positive bacteria are vulnerable to phage infiltration through peptidoglycan, while Gram-negative bacteria are targeted by lipopolysaccharides and pili. Bacteria defend against phages through physical barriers, CRISPR systems, and other mechanisms. Phage proteins stimulate immune responses and enhance antibiotic susceptibility. This review discusses phage attachment, entry, therapeutic use, and limitations of phage therapy. Phage-derived proteins and genetically engineered phages show potential in treating infections. Phages are classified into families based on morphology, with recent taxonomic changes. They have single-stranded or double-stranded DNA, RNA, or other genetic material. Phage specificity varies, with some infecting multiple strains. Phage-host interactions involve adsorption, entry, and immune evasion. Phages use various strategies to enter host cells, including tail fibers, pili, and exopolysaccharides. Some phages target cell wall structures, while others use plasmid-dependent mechanisms. Phage therapy has shown success in treating antibiotic-resistant infections, but challenges remain, including phage resistance, immune responses, and regulatory issues. Phage therapy has been used to treat multidrug-resistant infections, such as Acinetobacter baumanii and Pseudomonas aeruginosa. Phage cocktails have been effective against Mycobacterium abscessus in cystic fibrosis patients. However, resistance development and immune responses limit phage therapy. Phage-derived proteins, such as lysins and depolymerases, show potential in treating infections by degrading bacterial cell walls and biofilms. These proteins can enhance antibiotic efficacy and reduce biofilm formation. Phage-based therapies are being explored for use in medical devices to prevent biofilm formation. Despite their potential, phage therapy faces challenges, including immune system overstimulation and the risk of phage resistance. Phages are recognized by the immune system, and some studies show no significant immune response. Phage therapy is generally safe but requires further research to optimize its use. Phage-derived proteins and genetically engineered phages offer promising avenues for future treatments. However, more studies are needed to fully understand their therapeutic potential and to address the challenges associated with phage therapy.