There are many variations in the delivery of hemodialysis. These variations include components of conventional dialysis, such as membrane type, dialysis dose, and session duration. In addition, alternative approaches to dialysis, such as hemodiafiltration, nocturnal hemodialysis, and short daily hemodialysis, also may be considered. For some of these practice variations, data exist to support one approach over another (eg, fistulas rather than grafts and catheters), but for many, no such data exist. Very few practice variations have been examined in randomized trials, and we are reliant predominantly on observational data. This review examines some practice variations in hemodialysis delivery, attempting to highlight which of these may be appropriate to consider when optimizing dialysis delivery in the clinic.