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Most clinicians will agree that chronic constipation is characterized by abnormal bowel movement consistency and/or frequency plus or minus evacuation symptoms, but patient perception of constipation varies widely and includes symptoms that may or may not meet official defining criteria. Although intermittent constipation is extremely common, only a small minority of patients seek care for their symptoms. Among these patients, dissatisfaction with the currently available laxative options is not uncommon, and many patients will require specialized care for severe or refractory symptoms—especially those with abdominal pain, irritable bowel syndrome overlap, bloating or distention, and psychological comorbidities. This review outlines a physiological assessment of the patient with refractory constipation, exploring treatment options among patients with slow transit, rectal evacuation disorders, and normal transit. In addition, we explore nonlaxative approaches to normal-transit patients bothered by ongoing symptoms, with an emphasis on the biopsychosocial model of functional gastrointestinal disease and treatment of visceral hypersensitivity using neuromodulators. Finally, we propose a comprehensive evaluation algorithm for the management of patients with refractory slow-transit constipation considering surgery and examine surgical options including colectomy and cecostomy using an antegrade continent enema.