For decades, increasing incidence and prevalence of Crohn's disease (CD) have attracted more attention. Some severe complications such as perforations, fistulas, and abscesses have significantly impaired patients' quality of life. Though the emergence of biologic agents has improved disease course and prognosis to a great extent, different disease manifestations and the economic burden of disease make biologic agents not suitable for all CD patients. The ultimate goal of achieving clinical and endoscopic remission, and even transmural healing is same for every CD patient, but therapeutic decision is so difficult for individual differences. Making a personalized approach based on disease behavior, drug response and other related factors is critical for disease management. This review attempts to summarize the existing clinical trials and data for better tailoring personalized therapy of CD.