Treatment options for Crohn’s disease (CD) include conventional, largely generic small molecules and more-potent biological agents, including tumor necrosis factor-alpha (TNF-α) inhibitors. Despite the clinical and commercial success of the TNF-α inhibitors, opportunity remains for agents that can safely and effectively induce and maintain remission in a significant number of patients with moderate to severe CD, especially those refractory to TNF-α inhibitors. Indeed, with the launch of vedolizumab (Takeda’s Entyvio) in 2014, physicians have a welcome alternative for TNF-α inhibitor-refractory patients. Additional agents in late-stage development include therapies offering a variety of mechanisms of action; prominent candidates include the IL-12/IL-23 inhibitor ustekinumab (Janssen’s Stelara), the CAM inhibitor etrolizumab (Roche), and oral SMAD7 antisense oligonucleotide mongersen (Celgene’s GED-0301). The IL-12/IL-23 inhibitor ustekinumab, pending the release of additional Phase III data, has demonstrated efficacy in both TNF-α inhibitor-refractory and -naive patients. However, interviewed thought leaders do not expect any of these drugs to displace the TNF-α inhibitors as the dominant drug class for moderate to severe CD. The entry of less-expensive biosimilar TNF-α inhibitors and the increasingly difficult pricing and reimbursement environment will likely limit emerging agents’ market potential in the CD market.