Purpose of the Review <p>This review explores the direct and indirect interactions between bacteriophages and the human microbiome, aiming to clarify their complexities. It adopts a phage-centered perspective to examine how phage-microbe interactions shape microbiota composition, influence human health, and contribute to disease development. The review highlights the critical role of phages in microbial ecosystems and their significance in medical research.</p> Recent Findings <p>Recent studies show that bacteriophages significantly impact the composition and function of the human microbiome, influencing immune responses. The growing interest in phages as therapeutic agents is driven by the rise of multidrug-resistant bacteria and the increasing recognition of the gut microbiota’s role in health and disease prevention.</p> Summary <p>Bacteriophages, among the smallest microorganisms in the human body, play a vital role in shaping the microbiome and influencing health by applying selective pressure on bacterial populations. Present in various body regions, phages interact with mucosal surfaces and can cross epithelial layers. While they need specific host bacteria to disseminate, phages also modulate the immune system. The emergence of multidrug-resistant bacteria and the key role of the gut microbiota have reinvigorated interest in phages. This review explores the interactions between bacteriophages and the human microbiome and their effects on health and disease.</p>