Geographic clusters of high-technology companies are an increasingly important source of wealth and job creation in the advanced industrial countries. This article provides a framework for understanding the conditions that give rise to these self-sustaining high-skill ecosystems (HSEs) that is based on the cases of the highly successful biomedical and computer hardware and software firms clustered in Northern and Southern California. The framework identifies four requirements that HSEs share in common with natural ecosystems: a catalyst to trigger the start of their development, on-going nourishment, a supportive host environment, and a high degree of interdependence among the actors in the system. The framework is then applied to the UK, identifying those policy options that are necessary for gaining greater returns from the UK's strong research base.