Single-cell genomics provide researchers with tools to assess host-pathogen interactions at a resolution previously inaccessible. Transcriptome analysis, epigenome analysis, and immune profiling techniques allow for a better comprehension of the heterogeneity underlying both the host response and infectious agents. Here, we highlight technological advancements and data analysis workflows that increase our understanding of host-pathogen interactions at the single-cell level. We review various studies that have used these tools to better understand host-pathogen dynamics in a variety of infectious disease contexts, including viral, bacterial, and parasitic diseases. We conclude by discussing how single-cell genomics can advance our understanding of host-pathogen interactions.