Decades after the introduction of chronic maintenance hemodialysis, the optimal means of quantifying dialysis dose remains controversial. Differences of opinion in the international dialysis community lead to substantial diversity in everyday clinical practice. Several studies suggest that the well-recognized international mortality differences in hemodialysis populations may result from these divergent approaches to dialysis care. One of the main areas of divergence is the different degree of reliance on dialysis clearance when prescribing dialysis. The “clearance approach” implies that treatment quality is primarily dependent on efficient removal of uremic toxins as estimated by dialytic urea clearance. Urea can be rapidly removed by high efficiency dialysis in a relatively short time. The main alternative to this strategy is the “time approach” based on the recognition that longer or more frequent dialysis provides benefits beyond increasing urea removal. Some of the putative benefits are more effective volume and blood pressure control, better maintenance of hemodynamic stability because of slower ultrafiltration and removal of uremic toxins that do not behave like urea. Recently, chronic inflammation has been proposed to be an important predictor of outcome in dialysis patients. Inflammatory markers are commonly elevated in chronic renal failure and levels of these seem to correlate with malnutrition, maintenance of residual renal function, and volume control. The relationships between dialysis clearance, treatment time, chronic inflammation, volume control, and hemodynamic stability are explored in this review. We propose that a better understanding of these complex relationships may provide opportunities for improving outcomes of maintenance hemodialysis patients.