Thesis: This dissertation emphasizes the challenges raised by the management of rare diseases and is structured around three key actors of the diagnostic and therapeutic “odyssey” of patients with rare diseases. Part I is devoted to patients and their social networks. Chapter 1 considers demand-side sources of delay in receiving a diagnosis; Chapter 2 explores the health spillover effects from patients’ health to their direct support structure. Part II considers pharmaceutical firms and examines how firms’ decisions to allocate R&D investment to rare diseases are impacted by innovation policies in rare arenas. Chapter 3 evaluates the causal impact of the EU Orphan Drug policy on R&D efforts in orphan drugs, while Chapter 4 investigates the inequality in allocation of R&D investment within rare diseases. Part III focuses on policymakers and addresses the issues in measuring pharmaceutical innovation benefits along with costs in rare disease arenas, while considering the opportunity cost of healthcare expenditures. Chapter 5 measures the causal impact of pharmaceutical innovation in rare diseases on longevity, while Chapter 6 is a critical discussion of decision-making tools for rational allocation of healthcare resources, and the use of a cost-effectiveness threshold.