In order to develop novel solutions to avian disease problems, including novel vaccines and/or vaccine adjuvants, and the identification of disease resistance genes which can feed into conventional breeding programmes, it is necessary to gain a more thorough understanding of the avian immune response and how pathogens can subvert that response. Birds occupy the same habitats as mammals, have similar ranges of longevity and body mass, and face similar pathogen challenges, yet birds have a different repertoire of organs, cells, molecules and genes of the immune system compared to mammals. This review summarises the current state of knowledge of the chicken's immune response, highlighting differences in the bird compared to mammals, and discusses how the availability of the chicken genome sequence and the associated postgenomic technologies are contributing to these studies and also to the development of novel intervention strategies against avian and zoonotic disease.