Much of our knowledge regarding the interactions between epithelial tissues and the immune system has been gathered from animal models and co-cultures with cell lines. However, unique features of human cells cannot be modelled in mice, and cell lines are often transformed or genetically immortalized. Organoid technology has emerged as a powerful tool to maintain epithelial cells in a near-native state. In this Review, we discuss how organoids are being used in immunological research to understand the role of epithelial cell-immune cell interactions in tissue development and homeostasis, as well as in diseases such as cancer.