Entrepreneurship can promote economic performance in a variety of ways, short-term and in the longer run. A key finding of recent empirical studies is that high regional levels of entrepreneurship in terms of self-employment and new business formation tend to be rather persistent and can last for decades or even more than a century. A long tradition of regional entrepreneurship is often associated with certain mentalities and basic values of the population. Such a tradition or ‘culture’ of entrepreneurship can shape the ability of a regional economy to cope with external challenges such as national or global crises. I summarize research on long-term persistence and effects of entrepreneurship, discuss policy implications, and identify important avenues for further research.