Although glucose is still the most widely used osmotic agent for peritoneal dialysis, it has several disadvantages that challenge its long-term use. During the past years several nonglucose molecules have been tested as osmotic agents for peritoneal dialysis. Most of these molecules have some advantages over glucose, but they also have drawbacks. Every new agent should be carefully tested for performance and long-term safety. In the following review, alternative osmotic agents are discussed, including their potential indications and drawbacks. Major issues include the improvement of biocompatibility and preservation of peritoneal membrane integrity by using dialysate with more physiologic pH, the effect on nutritional status by using dialysate with amino acids, and maintenance of peritoneal ultrafiltration in the long-term by using dialysate with polyglucose. It is believed that in the near future, mixtures of osmotic agents will become most appropriate to obtain the best performance.