Cancer care in the United States faces a perfect storm: an aging population and expected increased cancer incidence, growing numbers of cancer survivors with ongoing care needs, and continued scientific advancements, offering extraordinary promise at extraordinary cost. How, then, do we as pediatric oncologists engage in the dialogue about cancer cost considerations? The purpose of this article and its accompanying session presented at the 2018 ASCO Annual Meeting is to introduce concepts of cost, value, and financial hardship. In the first section, we will provide an overview of principles of health economics, including components of cost, time horizon consideration, discounting, and methods to calculate incremental cost-effectiveness among therapeutic approaches. We will then introduce the value framework being debated in adult oncology and offer potential opportunities for its application in pediatric oncology. In the second section, we will describe the integration of the cost-effectiveness paradigm in an ongoing pediatric clinical trial, including design and analytic considerations. In the third section, we will shift away from cost to the health care system to cost to the patient, which is also termed "financial toxicity" or "financial hardship," focusing on the ongoing burden of cost on survivors of childhood cancer. Our goal is to provide our readers with the vocabulary and understanding of this complex and often thorny debate so that they can be active participants and informed advocates for their patients.