This is the first of two reports requested by the Social Security Administration (SSA) to address best practices and community experiences in the management and treatment of sickle cell disease (SCD). SCD, a group of inherited blood disorders affecting approximately 100,000 people in the United States, is a chronic, life-long condition that affects every organ system in the body. The life of an individual with SCD is often complicated by frequent bouts of extreme pain and hospitalizations, fatigue, organ damage, and mental health conditions. The cumulative burden of SCD-related health effects can significantly affect quality of life, including the ability to regularly attend and participate fully in school and work. In response to SSA's request, the National Academies of Sciences, Engineering, and Medicine convened an expert, ad hoc committee to review the latest published scientific research and generate findings and conclusions on a variety of topics related to SCD. This report is the first report in a two-report series, and presents the committee's findings and conclusions pertaining to SCD pain crises, pain management, and treatment settings relevant to SSA disability determinations.