Gastroenterologists will be all too familiar with the difficult decisions that managing inflammatory bowel disease often presents. How aggressively should I treat this patient? Do I expect them to have a mild or aggressive form of disease? Do they need a biologic? If so, which one? And when should I start it? The reality is that the answers that would be right for one patient might be disastrous for another. The growing therapeutic armamentarium will only make these decisions more difficult, and yet, we have seen how other specialties have begun to use the molecular heterogeneity in their diseases to provide some answers. Here, we review the progress that has been made in predicting the future for any given patient with inflammatory bowel disease—whether that is the course of disease that they will experience or whether or not they will respond to, or indeed tolerate, a particular therapy.