Preliminary introduced by Anselin, Varga and Acs (1997) spatial econometric tools are widely used in economic geography of innovation. Taking into account spatial autocorrelation and spatial heterogeneity of regional innovation, this paper analyzes how these techniques have improved the ability to quantify knowledge spillovers, to measure their spatial extent, and to explore the underlying mechanisms and especially the interactions between geographical and social distance. It is also argued that the recent developments of spatio-dynamic models opens new research lines to investigate the temporal dimension of both spatial knowledge flows and innovation networks, two issues that should rank high in the research agenda of the geography of innovation.