In a new review in Cell Host & Microbe, Jens Puschhof and Cayetano Pleguezuelos-Manzano, from the lab of Hans Clevers, describe advances in co-culturing microbes with intestinal and colonic epithelia. Organoid and organ-on-a-chip platforms in particular are compared to each other and to related models to evaluate the suitability of each for recapitulating host-microbe interactions, a key challenge in understanding the role of the microbiome in colon cancer.