The individual, societal, and economic benefits of disease prevention resulting from childhood and adult immunization programs in the United States are without question. A report from the Centers for Disease Control and Prevention (CDC) describing the benefits of vaccination of the 2009 birth cohort through 18 years of age estimated that 20 million cases of vaccine-preventable disease will not occur, 42 000 early deaths related to these diseases will be avoided, and $76 billion in direct and indirect costs will be averted. This economic benefit stands in stark contrast to the comparatively small cost for vaccine purchases. The estimated vaccine purchasing cost for a similar birth cohort based on 2015 pricing is $7.8 billion, based on CDC costs, and $11.6 billion at private sector pricing (eTable in the Supplement). Development of a novel vaccine is a risky and expensive endeavor with research, licensing, and production costs approaching or exceeding $1 billion.3 For a small company attempting to secure capital venture funding or for an established pharmaceutical company committed to developing innovative vaccines, expectation of a return on investment is essential. Pricing of licensed, newer vaccines generally far exceeds production costs, but revenue drives future vaccine development. The difficult question becomes what is a reasonable return on investment? The value of a vaccine to society should be based on reduction in health care costs and reduction in illness, pain, disability, and mortality. But how should value to society be balanced against pharmaceutical profit? A widely accepted standard on how to incorporate an economic analysis into deliberations regarding a vaccine recommendation is not available, and the threshold of how much society is willing to pay for a vaccine has proven difficult to define.