This chapter examines pricing and reimbursement (P&R) negotiations from the Payer/Government side with a negotiation eye. It describes in detail the structural and institutional challenges that increasingly make P&R negotiations harder for Governments and Payers. On the one hand, the populations are aging and suffering from more chronic illness. On the other hand, there are many more treatments (and treatment lines), higher expectations, and increasing drug prices. This leads to healthcare spending growing much faster than GDP in many countries when Governments struggle financially. The lack of funds begs the question of how to increase funding, who gets covered, by whom, and how to improve healthcare’s cost-efficiency. This chapter covers the ideas currently under discussion in the field through the eyes of negotiation and anticipating potential consequences.