Currently, about two-thirds of hemodialysis patients worldwide are treated with high-flux membranes. This is most likely based on the assumption that the extended solute clearance that can be obtained with more open membranes will contribute to improved clinical outcome. To have full advantage of convective solute removal, hemodiafiltration offers a superior modality as compared to both low-flux and high-flux hemodialysis. However, this technique is offered to only a minority of patients. In this review, we summarize the available clinical evidence on hemodiafiltration and define still remaining questions.