Advances in immune visualization have enabled the physical tracking of immune responses in vivo. The adaptation of such technology to models of infectious disease holds the promise of a more detailed analysis of host-pathogen interactions in a natural setting. However, the visualization of pathogen-specific immune responses in vivo confronts challenges that are inherent to the study of infectious disease systems. Recent attempts to track pathogen-specific immune responses in vivo validate the usefulness and underline the complexity of this experimental strategy.