The United States leads the world in many measures of health care innovation. However, it has been criticized to lag behind many developed nations in important health outcomes including mortality rates and higher health care costs. The surveys have shown the United States to outspend all other Organisation for Economic Co-operation and Development (OECD) countries with spending on health goods and services per person of $7,290 - almost 2(1/2) times the average of all OECD countries in 2007. Rising health care costs in the United States have been estimated to increase to 19.1% of gross domestic product (GDP) or $4.4 trillion by 2018. CER is defined as the generation and synthesis of evidence that compares the benefits and harms of alternate methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The, comparative effectiveness research (CER) has been touted by supporters with high expectations to resolve most ill effects of health care in the United States providing high quality, less expensive, universal health care. The efforts of CER in the United States date back to the late 1970s and it was officially inaugurated with the enactment of the Medicare Modernization Act (MMA). It has been rejuvenated with the American Recovery and Reinvestment Act (ARRA) of 2009 with an allocation of $1.1 billion. CER has been the basis of decision for health care in many other countries. Of all the available agencies, the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom is the most advanced, stable, and has provided significant evidence, though based on rigid and proscriptive economic and clinical formulas. While CER is taking a rapid surge in the United States, supporters and opponents are emerging expressing their views. Since interventional pain management is a new and evolving specialty, with ownership claimed by numerous organizations, at times it is felt as if it has many fathers and other times it becomes an orphan. Part 2 of this comprehensive review will provide facts, fallacies, and politics of CER along with discussion of potential outcomes, impact of CER on health care delivery, and implications for interventional pain management in the United States.