Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly. Hemodiafiltration (HDF) provides much higher convection rates, thereby reliably increasing the clearance of these larger toxins. However, the high ultrafiltration volumes employed by HDF significantly increase the concentration of proteins and lipids in the dialyzer blood compartment. This has the effect of increasing plasma viscosity, which opposes solute diffusion, and increasing plasma oncotic pressure, which opposes convection. The negatively charged plasma proteins also influence the equilibration of ions between dialysate and blood compartments. These effects result in varying conditions for solute transport along the length of the dialyzer and along the radial distance from the membrane within the dialyzer fibers. High-flux dialyzers can be designed to augment solute diffusion and internal filtration, so that their performance approaches that of HDF. This avoids some of the mechanical complexity of HDF, but such enhanced dialyzers may be more difficult to manufacture, control and monitor. Here, we present and discuss the most important physical phenomena associated with HDF therapy, providing an overview of its main concepts and principles. In particular, we discuss the physics of solute diffusion and convection and the factors affecting them, and we compare predilution or postdilution HDF with enhanced HD.