<p>Determining the host range is a fundamental step in characterizing newly isolated phages, as it not only guides their use in therapy and in biocontrol applications but also helps in managing their impact on bioprocesses. Host specificity is typically evaluated through experimental assessment of host cell lysis, but the underlying molecular mechanisms that define host range are rarely explored in a comprehensive manner. Interactions between viral proteins and bacterial surface receptors during adsorption have historically been viewed as the primary determinants of host specificity. However, advances in cataloguing the diversity of bacterial defence systems emphasize that host range is shaped by a complex interplay of phage–host interactions, phage–phage interactions and environmental factors. Moreover, host range is dynamic, being influenced by ongoing coevolution between phages and bacteria as well as by phenotypic variability. As tools are now being developed to predict phage host range at the strain level from genomic data, a deep understanding of the diverse, dynamic factors that shape this host range is essential. In this Review, we provide an integrated perspective on the molecular and ecological determinants of phage host range, explore their dynamics and discuss the implications for phage-based applications.</p>