Midodrine is an alpha-agonist that causes peripheral vasoconstriction, resulting in increased blood pressure. It has been reported to be safe and effective in patients with end stage renal disease (ESRD) and is widely used for hemodialysis-associated hypotension. We report a case report of midodrine-induced ischemia in a patient on hemodialysis and review the literature relating to the safety of midodrine in patients with end stage renal disease.