In a Phase 2 placebo-controlled trial, low dose naltrexone (LDN) improved inflammation of the gastrointestinal mucosa and improved clinical activity scores in patients with mild to moderate Crohn’s disease (CD). We present two patients with symptomatic CD with a rapid clinical and endoscopic response to LDN: 1) Crohn’s colitis with prolonged maintenance to LDN which had failed mesalamine with immunomodulator therapy; and 2) Crohn’s ileitis with prolonged remission with addition of LDN to biologic and immunomodulator therapy.