Organoids are three-dimensional culture systems that resemble their organ of origin, are genetically stable, and can phenocopy diseases. They enable modeling of various cancer entities such as gastric or colorectal cancer, in addition to other gastrointestinal tract diseases such as inflammatory bowel disease. Genetic engineering tools like CRISPR/Cas9 allow their manipulation to repair mutations or unravel gene functions. Individual patient-derived organoids allow to test therapies in vitro before their in vivo application, bringing personalized medicine to a next level. Organoid biobanks can be used to conduct drug screenings and validate biomarkers. Interactions with microbiota can be investigated in realistic in vitro models. Transplantability of genetically engineered organoids opens up new avenues in the tissue engineering research field. Organoid cultures thus represent a versatile system to model diseases and test therapeutic interventions.