It is increasingly recognized that infection, disease, and immunity involve a complex web of interactions between pathogen and host, an interaction that is best tackled with the science of Systems Biology. In this talk I will first briefly outline what systems the principles of systems biology. I will go on to describe our systems-based TB research in two areas: firstly examining the exchange of nutrients between the TB bacillus and its host cell, the macrophage in order to identify potential drug targets. In the second part of this talk, I will describe our systems-based approaches to designing novel vaccine/diagnostic test approaches for control of bovine tuberculosis.