Since the widespread introduction of peritoneal dialysis (PD) into the standard care of patients with chronic kidney disease there has been a shift from the initial focus on technique survival to refinement of the therapy to enhance biocompatibility and improve both the local peritoneal and systemic consequences of PD. One of the most significant contributions to these advances has been the development of novel PD solutions. The use of new manufacturing techniques, buffer presentation, and new osmotic alternatives to glucose have allowed potentially improved peritoneal survival (in terms of structure and function) and improved subjective patient experience. Additional benefits have also included, enhanced management of salt and water removal, supported nutritional status and improvement in the systemic metabolic derangements associated with conventional PD treatment, based on glucose-containing lactate-buffered solutions. The selection of suitable targets for modulation of therapy continues to be hampered by our continued relative ignorance of the local and particularly systemic effects of PD compounded by the dearth of quality, outcome-based studies. The aim of this review is to summarize the characteristics of the next generation of PD fluids currently available, and then to evaluate their possible place in treatment by considering the difference in their effects in a series of structural and functional areas potentially relevant to improving patient outcomes.