For decades plagued by therapies of limited efficacy, the recent arrival of an embarrassment of riches in effective therapeutics for inflammatory bowel disease (IBD)1,2—likely to grow further in coming years3-6—has made personalization of therapy ever more urgent. Practicing physicians have no other option than to follow a rather mundane step-up and trial-and-error approach. The results of an exemplary biomarker trial conducted by Janssen and published in this issue of Gastroenterology7 showcases how hard progress in this area is and points to the sobering prospect that the current trial-and-error approach may stay for some longer.