Background: Knowledge of payer evidence requirements is vital to manufacturers who are facing increasing development costs for uncertain market access outcomes. Failure to engage payers early in asset development could result in delay of approval and/or coverage. Objectives:Build the case for early payer engagement as a means of reconciling the needs of payers and manufacturers. Method: A literature search was performed and primary research with key opinion leaders in the US and EU was conducted to characterize 5 early engagement strategies (informal consultation, formal consultation, outcomes-based risk sharing, financial-based risk sharing, and formal partnerships). 7 major markets (Canada, France, Italy, Germany, Spain, UK, and US) were also assessed for their historic use of early engagement models. Results: Payers want more manufacturer involvement in evidence development, including input into clinical trial design and RWE development in phases II and III through formal and informal consultations. Articulation of an asset’s value story in the peri-launch phase and negotiations with regional and local payers through direct consultations allows manufacturers to position the asset for optimal pricing and reimbursement. When agreement cannot be reached on price or reimbursement terms, risk-sharing agreements allow broader access in exchange for the manufacturer bearing incrementally greater financial risk. Manufacturers have also built partnerships to uncover the real-world value of therapies and gain insight into usage and adherence patterns. Each market has its own challenges for promoting collaboration, requiring manufacturers to tailor their approach to the various national and local payers. Conclusion: Early planning is imperative in value-focused health care. When early payer engagement succeeds, it provides manufacturers time to design informed strategies to meet payer valuation needs. Evidence development that is closely aligned with payer requirements results in therapies that are more cost effective and gain quicker market access, benefitting manufacturers, payers, and patients alike.