Technological concentration and innovation have been identified as important forces behind growth, and entrepreneurship has been recognized as an important link between new knowledge and economic growth. This article examines the influence of entrepreneurship and technology concentration on employment growth in U.S. metropolitan areas (MSAs) over the course of the last full business cycle from 1991 to 2007. The findings are in support of the efficacy of entrepreneurship together with high technology expansion in job creation. The findings question the view that entrepreneurship in and of itself, or a high but not growing high technology concentration, can be strong contributors to employment growth. In contrast, this analysis indicates that MSAs with growing high-tech activities and above-average entrepreneurship can be expected to add jobs much faster than other MSAs. The findings suggest a need for a more targeted approach to economic development and job creation.