The recent proliferation of value assessment frameworks for innovative medicines, proposing a range of approaches and methods, has confused many potential users. This policy analysis explores their differences and similarities, and the implications for regulatory and related types of health technology assessment. Approach: We review the objectives and methods of seven different value frameworks including those of the American Society of Clinical Oncology (ASCO), the Institute for Clinical and Economic Research (ICER), and the National Comprehensive Cancer Network (NCCN), and four others. Findings: We find that these frameworks differ substantially in their place and role in the health care system—their “decision context.” Some (e.g., ASCO, NCCN) aim to support clinical shared decision-making. Others (e.g., NCCN) support the development of treatment guidelines and clinical pathways. Finally, others (e.g. ICER) support decisions about inclusion and reimbursement in the health plan benefit package. Clinical value in regulatory benefit-risk balance is a fourth decision context. Net health benefit (NHB) is the key element that links the decisions in this hierarchy of decisions. Regulators judge NHB (benefit-risk balance). Payers assess whether the NHB is worth any additional cost. Health plan managers develop guidelines, pathways, and utilization management tools (e.g., prior authorization), considering both NHB and cost, to provide efficient stewardship of health plan resources. At the shared decision-making level, the focus should be on the physician as the agent helping the patient to assess their individual, tailored NMB based on individual health state preferences. We argue that the four key decision contexts—regulatory benefit-risk analysis, coverage and reimbursement, treatment guidelines and clinical pathways, and clinical shared decision-making—can be aligned by using the QALY as a central value element in each of these related decision contexts, augmented by other value elements, such as insurance value and the value of knowing.