Pyoderma gangrenosum is a neutrophilic dermatosis that is rare in infancy, with only 20 cases reported in the literature. We present a case of infantile pyoderma gangrenosum refractory to topical steroids, tacrolimus, and dapsone as well as systemic steroids and infliximab that is currently well controlled with the addition of oral tacrolimus. To our knowledge, this is the first report of the effective, safe use of oral tacrolimus in combination with infliximab for infantile pyoderma gangrenosum. We review all current cases of infantile pyoderma gangrenosum, as well as tacrolimus and its role in the treatment of this condition.