ABSTRACT The traditional view of immune cells is that their role within the body is to combat infections; however, it is becoming increasingly clear that they also perform tasks that are not classically associated with inflammation and pathogen clearance. These functions are executed deep within tissues, which are often poorly accessible and subject to environmental variability, especially in humans. Here, we discuss how multicellular 3D systems in a dish – organoids – are transitioning from a proof-of-principle approach to a timely, robust and reliable tool. Although we primarily focus on recent findings enabled by intestinal organoids co-cultured with lymphocytes, we posit that organoid co-culture systems will support future efforts to disentangle the interactions between a plethora of different cell types throughout development, homeostasis, regeneration and disease.