Crohn's disease (CD) is a chronic, progressive, and debilitating disease characterized by inflammation of the gastrointestinal tract. It can have a significant impact on quality of life if not adequately controlled by appropriate treatment. In recent years, disease management strategies for CD have evolved from a focus on treating symptoms toward the additional goal of early treatment to modify disease progression and prevent bowel damage. Advanced therapies, including biologics, are a key part of the modern medical treatment paradigm for CD, but their introduction has made the treatment landscape more complex. Knowing which advanced therapy to use, when, and for which patient is challenging for health care providers. The alpha4beta7 integrin inhibitor vedolizumab has demonstrated effectiveness, tolerability, and an acceptable long-term safety profile in patients with CD. In this review, we discuss the use of vedolizumab in the management of CD to help clinicians make evidence-based treatment decisions and maximize benefits for their patients. We summarize the medical management of CD, the unique gut-selective mechanism of action of vedolizumab, and the current clinical guidelines for using vedolizumab in patients with CD. We detail the ability of vedolizumab to achieve mucosal healing and alter disease progression and present the evidence that supports the use of vedolizumab as a first-line biologic early in the disease course in patients with CD. Finally, we address some of the perceived drawbacks of using vedolizumab in CD, including concerns about slow onset of action, impact of disease location, and exacerbation of extraintestinal manifestations.