Theoretical immunology is the application of mathematical modeling to diverse aspects of immunology. Immunoinformatics, the application of computational informatics to the study of immunological macromolecules, addresses questions in immunobiology and vaccinology, as well as addressing issues of data management, and can design and implement new experimental strategies. Artificial Immune Systems (AIS) uses ideas and concepts from immunology to guide and inspire new algorithms, data structures, and software development. These three different disciplines are now poised to engineer a paradigm shift from hypothesis- to data-driven research, with new understanding emerging from the analysis of complex datasets: theoretical immunology, immunoinformatics, and Artificial Immune Systems (AIS). 'in silico Immunology' will summarize these emergent disciplines and will address the issue of synergy as it shows how these three are set to transform immunological science and the future of health care.