In the perpetual battle against common poultry pathogens and other environmental antigens, the role of the immune system is an important and ongoing topic of research. This chapter reviews the various elements of the host defence system in poultry, and then provides specific examples of how certain supplements can modulate the immune system and its responses to specific challenges that are common in commercial production. The chapter focuses particularly on the challenge of coccidiosis and the role of probiotics, and looks ahead to future developments in this area.