Hyponatremia is the most common electrolyte abnormality seen in clinical practice. Most cases of euvolemic or hypervolemic hyponatremia involve arginine vasopressin (AVP). AVP leads to a concentrated urine and negative free water clearance. Given this primary role of AVP, antagonizing its effect through blockade of its receptor in the distal tubule is an attractive therapeutic target. Lixivaptan is a newer, non-peptide, vasopressin type 2 receptor antagonist. Recent studies have demonstrated efficacy. This review summarizes the clinical pharmacology and data for this new agent.