The interaction between both beneficial and pathogenic microbes and their host has been the subject of many studies. Although the field of systems biology is rapidly evolving, the use of a systems biology approach by means of high-throughput techniques to study host-microbe interactions is just beginning to be explored. In this review, we discuss some of the most recently developed high-throughput 'omics' techniques and their use in the context of host-microbe interaction. Moreover, we highlight studies combining several techniques that are pioneering the integration of 'omics' data related to host-microbe interactions. Finally, we list the major challenges ahead for successful systems biology research on host-microbe interactions.