Eradication initiatives offer important opportunities to provide global as well as intergenerational health benefits. Humankind should aspire to the eradication of diseases; however, the decision to commit to an eradication goal should derive from careful consideration of the evidence base and a thorough discussion of the benefits, risks, and costs of eradication compared to the status quo. This chapter discusses the need to develop an eradication investment case (EIC) as a tool to support the decision-making process involved in launching an eradication initiative. Eradication initiatives, like other major societal investments (e.g., capital and infrastructure investments), require careful and deliberate conception and management. Benefits from eradication may include the public good of intergenerational health and associated productivity gains and/or economic savings. However, like other major projects, eradication initiatives represent resource-intensive efforts with associated opportunity costs. Proponents of future eradication initiatives should develop an investment case prior to launch. Critical elements of an EIC are discussed, and the need to standardize the methodology to the greatest extent possible is identified. Since no single overarching decision-making body currently exists to demand and review EICs, an analytic-deliberative process must be developed. The EIC should support and inform deliberations and decisions made by national health leaders at the World Health Assembly and elsewhere, as they consider a global commitment to an eradication goal. An EIC will also stimulate the development of a financial plan, which will provide details about financing the initiative, as stakeholders evaluate the choice to commit to an eradication goal. The EIC will not, however, include the financial or fundraising plan. Innovation should lead to the creation of additional mechanisms to finance eradication initiatives, perhaps including the use of an " eradication bond." Issues of phasing and timing of multiple eradication initiatives are discussed, as is the need to consider potential synergies of eradication initiatives and opportunities to diversify the disease eradication portfolio.