Imaging techniques have been revolutionized by advancements in both microscope instrumentation and data collection processing software. Immunologists and microbiologists now have access to a large panel of powerful technologies that are characterized by different spatial and time resolutions. In this review, we discuss recent studies in which emerging imaging technologies have been used to decipher the complexity of the interactions between pathogens and their mammalian hosts. By focusing on two very different pathogens, Plasmodium and Salmonella, we emphasize the critical role of imaging studies in the understanding of the host's immune system response to a pathogen.