A major current challenge in achieving sustainable poultry production is reducing risk to animal and human health. Strategies to control poultry diseases utilise selective breeding to enhance immunity and disease resistance. However, immune and disease resistance traits are difficult to measure, moderately heritable and of complex polygenic architecture. Consequently, only recently have poultry breeding programmes addressed health related traits. This chapter discusses the advances in genetic, genomic and functional genomic studies of immune and disease resistance in chickens and the role of the MHC. It reviews multi-trait selection experiments and discuss potential trade-offs between production and immunocompetence and the response to disease. These reveal significant genetic variation, in specific loci playing an important role in immune and disease resistance traits, however, further interdisciplinary studies are required to elucidate the underlying mechanisms. In conclusion, selective breeding has the potential to provide an accurate, environmentally friendly and cost-effective approach to disease control.