This paper initiates the start of a research process of knowledge clusters definition, main prerequisites for their establishment, formation stages and key participants. It presents one example of a knowledge cluster in Spain, by describing its establishment process, main participants and mechanisms of functioning. The author describes some of the projects and initiatives in the field of knowledge cluster formations in Bulgaria. On the base of the literature review and the Bulgarian experience in that area, some conclusions are drawn. The author states that this article raises more questions than giving certain answers. It also reveals a broad arena for future research work.