This chapter is about a special form of virtual organization: the Public-Private Partnership (PPP), created for the purpose of generating new knowledge. PPPs typically consist of three types of partners: academia (universities and affiliated institutions), industry (individual companies) and government (departments or agencies). The PPP delivers knowledge to its participants. At the same time, the participants provide input to the PPP (e.g., knowledge, user demands or policy goals), each in their own way. PPPs show considerable variation in the number of participants, budgets, life span and the areas of research they cover. Furthermore, they can differ in scale (multinational, national or regional) or in the type of partner that takes the initiative or lead. In some cases, a separate, intermediate organization will initiate, facilitate and stimulate the cooperation. A major issue in any PPP is the value of the knowledge that is (or will be) generated. To be more precise, the real issue is the valuation of knowledge: What beliefs and assumptions do the partners have about this value? What models or calculations do they use to find out what the knowledge is really worth to them? What makes them decide to invest money and time? This chapter will provide insight into the valuation process and the typical differences between the three types of partners in this respect. The insight will help to explain why some PPPs fail or malfunction, and it offers a set of basic conditions that must be met to run a PPP successfully. Finally, and perhaps most important, it may help to identify and overcome the cultural barriers between the partners and the misunderstandings that result from them. This is useful for anyone who finds himself involved in a PPP, and especially for those who set up and manage it, or plan to do so.