In order to understand the integrated behavior of the immune system, there is no alternative to mathematical modeling. In addition, the advent of experimental tools such as gene arrays and proteomics poses new challenges to immunologists who are now faced with more information than can be readily incorporated into existing paradigms of immunity. We review here our ongoing efforts to develop mathematical models of immune responses to infectious disease, highlight a new modeling approach that is more accessible to immunologists, and describe new ways to analyze microarray data. These are collaborative studies between experimental immunologists, mathematicians, and computer scientists.