Study of the importance of the microbiome to health and susceptibility to diseases has become a leading area of research in poultry science in recent years. The microbiota is emerging as a fundamental force influencing diverse aspects of avian physiology. This chapter examines intestinal immunity and microbiota interactions with the immune system. The chapter considers the role of gut microbiota as an epigenetic regulator of gut function as well as the causes of dysregulation of gut functionality. Finally, the chapter looks ahead to future research trends in this area.