There is a strong biological plausibility for benefit from removal of larger uremic toxins and increasing positive clinical experience with hemodiafiltration. However, evidence supporting hemodiafiltration is not definitive with studies that are often limited by serious methodological shortcomings. Morena et al. show that hemodiafiltration may prevent intradialytic hypotension, albeit in a study that also has some shortcomings. Ongoing research for hemodiafiltration is still needed through high-quality clinical trials that adhere to standards for clinical trial conduct and reporting.