This article considers the current state of the innovation development on the territory of Kaliningrad region its agents, main fields of operation, problems and perspectives. The major constraints to the innovative development of Kaliningrad region are held to be institutional: the dependence of the regional economy on the political and administrative controls of the federal center; the excessive government role in the regulation of economic processes, while there is no protection from the economic risks associated with doing innovative entrepreneurship; the strategic uncertainty regarding the future of the region. Among the key agents of the innovation development, the article identifies three groups of the innovation entities: large companies, government and universities. Generally, in the region, after a period of decreased cooperation activity of the regional authorities with the universities there is a marked trend towards the development of cooperation. The interaction of the entities of the innovative activity in the region is currently at the stage of institutionalization: entities select the best practices, define organizational formats of the interaction, develop conventional forms of cooperation and formalize them. To sum up, the paper offers a set of practical measures to promote innovative development in the region.