Overall prognosis research concerns the description of average future outcomes of groups of people with a certain disease or health condition in the context, time, and setting of current healthcare. This chapter describes how overall prognosis is estimated among people with a defined health condition in relation to relevant health outcomes. Study design, from newly designed prospective cohorts to cohorts embedded in routine healthcare data, is discussed. The value of information derived from overall prognosis research for patients and for healthcare professionals, policymakers, and funders, is considered, particularly in relation to decision making in healthcare practice and to monitoring healthcare outcomes for policymaking. Wider roles of overall prognosis estimation in informing other types of prognosis research, the design and interpretation of treatment effectiveness studies, understanding the consequences of using new diagnostic tests, and identifying unintended benefits or harms of treatment, are described.