Innovation is an essential cornerstone of human development. Throughout history, humans have created an infinite amount of innovations, ranging from early hunting tools to modern technologies. In principle, innovation have improved human lives (e.g. advances in the life sciences and increasing life expectancy) and are a fundamental building block of economic development. However, economic development is not equal across all regions, as some regions tend to grow faster and at higher rates while others suffer from long periods of decline. Research in economic geography has linked these regional differences in economic growth with the innovation capacity in regions, as innovation do not occur anywhere at the same rate, but rather concentrate in specific places. To explain regional differences, knowledge usually enters models of knowledge production or economic development as a quantity without considering differences in the quality of knowledge. Research from various disciplines, however, emphasizes that knowledge is not alike, but shows substantial differences regarding quality. Some innovations stand out in the history of innovations, as they reshape existing paradigms (e.g. Copernican Revolution, Einstein’s Theory of Relativity), change the pace of life (e.g. the printing press, the telephone, the internet), or reset technological boundaries (e.g. satellites, quantum computing). In fact, the literature provides a range of dimensions along which knowledge quality can be differentiated. For instance, new knowledge production relies on the combination of existing knowledge. Relatedness highlights that not every technology, or more general, any knowledge pieces can be combined with the same efforts and with the same success. Relatedness between technologies facilitates effective communication and learning and reduces uncertainties and risks. Alternatively, knowledge differs in its underlying complexity. Advancing and connecting the multitude of different technologies required for the moon landing might have been more complex than developing the PageRank algorithm for Google’s search engine (Fleming and Sorenson 2001). Knowledge also varies in its degree of novelty. Some inventions introduce radically new products or processes such as Gutenberg’s printing press, whereas others add marginal improvements or represent incremental modifications. Knowledge is also heterogeneous in its impact on the economy, society, and technology. The invention of the first automobile by Daimler and Benz or the first powered flyer of the Wright brothers lead to the emergence of new industries and reshaped existing technological paradigms. Other inventions do not even become innovations. Hence, (a) relatedness, (b) complexity, (c) degree of novelty, and (d) impact represent four important dimensions of knowledge quality, which the present thesis centers on. The findings of this thesis reveal that knowledge quality varies substantially between regions. The heterogeneity of places is not only important for differences in the production of new knowledge in pure quantitative terms, as often highlighted in previous research, but also crucially important to explain differences between places regarding the quality of new knowledge. Moreover, these qualitative differences of knowledge production between regions are crucial to explain the uneven development of places, for instance, in terms of economic growth and collective learning.