Technical Abstract: With increasing consumer¿s demands for safe poultry products, effective control of disease-causing pathogens is becoming a major challenge to the poultry industry. Many chicken pathogens enter the host through the gastrointestinal tract, and over the past few decades in-feed antibiotics and active vaccination have been the two main mechanisms of disease control. However, increasing public concerns are prompting government regulations on the use of growth promoting drugs in animal production, and the ability of current vaccines to protect against emerging hypervirulent strains of pathogens is becoming an issue. Therefore, there is a need to develop alternative control strategies against poultry pathogens of economic importance, as well as to carry out basic research to enhance understanding of host-pathogen interactions at local sites of infection. Effective control strategies against pathogens can only be accomplished by comprehensive analysis of the basic immunobiology of host-pathogen interactions. Recent sequencing of the poultry genome and the availability of several tissue-specific cDNA microarrays are facilitating the rapid application of functional immunogenomic technologies to poultry disease research. Studies using functional genomic, immunology and bioinformatic approaches have provided novel insights into disease processes and protective immunity to chicken pathogens. In this review, we summarize recent published literature concerning the host response to Eimeria and Salmonella infections with emphasis on our studies using immunogenomic tools to investigate and characterize the mechanisms of avian immunity to these mucosal pathogens. The results clearly indicate that this immunogenomic approach will lead to increased understanding of immune responses to infectious agents that will enable the development of effective prevention strategies against mucosal pathogens.