Background: Icodextrin is a peritoneal dialysis solution that is commonly used to increase ultrafiltration during the long dwell. The other major clinical benefit of icodextrin is that it is glucose-sparing, which may help preserve peritoneal membrane function. Since it has a different chemical composition than dextrose, and with its increasing use, there are several clinical considerations healthcare providers must familiarize themselves with prior to prescribing icodextrin. Summary: Failure to recognize these special properties of icodextrin can lead to adverse events reaching patients. This narrative review explores the hemodynamic, metabolic, and idiopathic effects of icodextrin to facilitate the safe use of icodextrin in peritoneal dialysis. Key Messages: Hemodynamic effects include hypotension from enhanced ultrafiltration contributing to loss of residual kidney function. Metabolic effects include the chemical structure of icodextrin interfering with biochemical assays, resulting in misleading glucose readings on non-specific glucometers. Idiopathic adverse effects include a diffuse rash and sterile peritonitis. It is also important to remember that not all antibiotic combinations have undergone stability testing in icodextrin. This narrative review will help healthcare providers to confidently prescribe icodextrin to maximize its benefit in peritoneal dialysis patients.