Previously, clinicians have had few choices in treating mild to moderate Crohn's disease. They currently treat these Crohn's disease patients with oral mesalamine and antibiotics. This treatment approach is based on the safety of these agents, and the perception that they are effective. This perception regarding efficacy may be influenced by publication bias. This review examines the efficacy and safety data of the conventional corticosteroids, mesalamine, sulfasalazine, budesonide and antibiotics for inducing the remission of mild to moderate Crohn's disease from randomized controlled trials, and proposes an evidence-based treatment approach. Sulfasalazine has demonstrated modest efficacy when Crohn's disease is confined to the colon. Mesalamine has no clear benefit over placebo in treating active Crohn's disease. Conventional corticosteroids effectively induce remission but are associated with unwanted adverse effects. Budesonide has similar efficacy to conventional steroids with far fewer adverse effects. Antibiotics have not consistently demonstrated efficacy. We propose a new evidence-based approach which suggests inducing remission of mild to moderate Crohn's disease with budesonide 9 mg/day for patients with ileal and/or right colonic involvement; sulfasalazine for those with disease limited to the colon; and conventional steroids for high disease activity, those who failed budesonide and those with left-sided disease who are allergic or intolerant to sulfasalazine.