Delivered dose of hemodialysis has long been an important predictor of mortality. The limitations of conventional hemodialysis treatments have led to a renewed interest in more frequent and longer hemodialysis treatments. As alternative hemodialysis schedules have become more prevalent, a need for modified metrics to measure adequacy has emerged. In addition, there is an interest in finding measures of hemodialysis adequacy that are more reliable in certain subgroups of patients, such as women, ethnic minority groups, or people with small body size. Finally, extended hemodialysis schedules suggest a need for metrics that can measure the clearance of solutes other than urea, such as middle-size molecules, and solutes for which clearance depends on intercompartmental transport across membranes. New metrics to quantify clearance in extended and alternate hemodialysis schedules are needed. As new metrics are developed, it is anticipated that they will also contribute to more accurate assessments of associations between clinical outcomes and delivered dose of dialysis in more intensive, nontraditional hemodialysis schedules. This review provides a historical prospective of dialysis dose and adequacy and describes the need for new metrics from both solute type and dialysis dose prospective as alternative hemodialysis schedules have emerged and become more prevalent.