Online hemodiafiltration (HDF) is an established renal replacement modality for patients with end stage chronic kidney disease that is now gaining rapid clinical acceptance worldwide. Currently, there is a growing body of evidence indicating that treatment with HDF is associated with better outcomes and reduced cardiovascular mortality for dialysis patients. In this comprehensive review, we provide an update on the potential mechanisms which may improve survival in HDF treated patients. The strongest evidence is for better hemodynamic stability and reduced endothelial dysfunction associated with HDF treatments. Clinically, this is marked by a reduced incidence of intradialytic hypotensive episodes, with a better hemodynamic response to ultrafiltration, mediated by an increase in total peripheral vascular resistance and extra-vascular fluid recruitment, most likely driven by the negative thermal balance associated with online HDF therapy. In addition, endothelial function appears to be improved due to a combination of a reduction of the inflammatory and oxidative stress complex syndrome and exposure to circulating cardiovascular uremic toxins. Reports of reversed cardiovascular remodeling effects with HDF may be confounded by volume and blood pressure management, which are strongly linked to center clinical practices. Currently, treatment with HDF appears to improve the survival of dialysis patients predominantly due to a reduction in their cardiovascular burden, and this reduction is linked to the sessional convection volume exchanged.