CO oxidation, although seemingly a simple chemical reaction, provides us with a panacea that reveals the richness and beauty of heterogeneous catalysis. The Fritz Haber Institute is a place where a multidisciplinary approach to study the course of such a heterogeneous reaction can be generated in house. Research at the institute is primarily curiosity driven, which is reflected in the five sections comprising this Review. We use an approach based on microscopic concepts to study the interaction of simple molecules with well-defined materials, such as clusters in the gas phase or solid surfaces. This approach often asks for the development of new methods, tools, and materials to prove them, and it is exactly this aspect, both, with respect to experiment and theory, that is a trade mark of our institute. The best reference: The enormous progress in the elementary understanding of heterogeneous catalysis is based to a large degree on the study of CO oxidation as a probe reaction of heterogeneous processes. Experimental and theoretical results from this seemingly simple reaction are presented and it will be shown how these can be used to draw general conclusions about heterogeneous reactions © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.