Liver disease is estimated to develop in 40% to 60% of infants on long-term parenteral nutrition (PN) secondary to intestinal failure. The etiology of intestinal failure-associated liver disease (IFALD) is multifactorial with primary contributors including prematurity, sepsis, deficiencies or hepatotoxicities of infusates, and lack of enterally stimulated bile flow. IFALD treatment strategies have historically emphasized the following: choleretics such as ursodeoxycholic acid, bowel decontamination for small bowel bacterial overgrowth, bowel tapering and lengthening procedures, and manipulations of PN prescriptions (e.g., cycling). This review highlights current and proposed novel treatment and management strategies for IFALD. These include a discussion of state-of-the art central line care practices, novel bowel-lengthening procedures such as serial transverse enteroplasty, isolated liver transplant for IFALD, probiotics and glutamine for bowel decontamination, hormonal therapies for achieving bowel adaptation, and a discussion of new PN formulations that may have emerging roles in IFALD.