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Digestive cancers are a major cause of mortality worldwide. The two major recent breakthroughs in oncology – targeted therapies and immunotherapies – having only led to marginal therapeutic advances in digestive oncology, cytotoxic chemotherapy remains the mainstay of treatment of these cancers. Moreover, there is no standard treatment beyond the second or third line for most of digestive, non-colorectal cancers. Thus, there is an urgent unmet need to develop personalized medicine approaches for patients with advanced digestive cancers.Organoids are a promising tool for personalized medicine strategies. Grown from stem cells, organoids are tridimensional multicellular structures, cultivable ex vivo, that retain genotypic and phenotypic characteristics of their primary tissue or tumor of origin. Carcinoma-derived organoids are generated from biopsies or surgically resected tumors. These structures are now recognized as ex vivo avatars of physiological and pathological tissues, and open important perspectives for biomedical and clinical research.We present here an overview of digestive tissue- and tumor-derived organoids, as a model for the comprehension of digestive tumors and basic research. Then, we discuss the applicability of organoids in the clinic in innovative precision medicine strategies.