Nocturnal polyuria (NP), characterized by overproduction of urine at night (greater than 20%-33% of total 24-hour urine volume depending on age), is a major contributing factor in most nocturia cases. Nocturia can be caused by intake, urological, nephrological, hormonal, sleep, and cardiovascular factors. It is therefore important to accurately diagnose both the type of nocturia and the potentially associated medical conditions to determine appropriate treatment. Diagnostic tools, in addition to a thorough history and physical examination, include voiding/bladder diary analyses and questionnaires to diagnose nocturia type (NP, diminished nocturnal/global bladder capacity, global polyuria) and causative factors. Lifestyle modifications are the first intervention implemented for the management of nocturia and NP but, as symptoms progress, such measures may be insufficient, and pharmacotherapy may be initiated. While drugs for benign prostatic hyperplasia and overactive bladder have demonstrated statistically significant reductions in nocturnal voids, patients often fail to achieve a clinically meaningful response. Antidiuretic treatment is warranted for patients with nocturia due to NP because, in many patients, it treats the underlying cause (ie, insufficient secretion of antidiuretic hormone arginine vasopressin) that leads to overproduction of urine at night and has been shown to provide statistically significant reductions in nocturnal voids. Desmopressin, a synthetic analog of arginine vasopressin, is the only antidiuretic treatment indicated specifically for nocturia due to NP. Overall, the pathophysiology of NP is complex and differs from that of other types of nocturia. A multidisciplinary approach is necessary to effectively diagnose and manage this bothersome condition.