In this article we provide a contemporary overview of available clinical data on certolizumab pegol, a pegylated anti-tumor necrosis factor (TNF) alpha agent that comprises a uniquely small protein, and its emerging role as a therapy for Crohn’s disease (CD). The results from a comprehensive clinical trial program suggest that certolizumab pegol offers rapid and sustained remission of moderate to severe CD. Certolizumab pegol is an effective and well-tolerated therapy both in patients who have already received biologics and in patients who are anti-TNF naïve. Benefits of therapy include a stable dosing regimen, which allows for rapid induction of a clinical response followed by long-term maintenance of response and remission under one fixed dose. Treatment with certolizumab pegol has been shown to improve function and quality of life in patients with CD, and insights into the potential mechanisms by which certolizumab pegol effects a response in CD suggest that this agent may have the potential to slow or even modify disease progression. Early therapy is particularly effective and could help control CD progression and lessen the burden of disease on patients.