Focusing on emerging technology regions of the US, Canada and Mexico, the authors provide an analysis of firms' innovative milieus in three contexts: national systems of innovation, knowledge regions and incubation mechanisms. An overview of the evolution of each region over the past quarter century is presented, along with an evaluation of the effectiveness of science parks and technology incubators in various regional and national environments. Though the three countries studied share the same continent and have well-developed trade relations, the significant differences between them in level of development, industrial infrastructure, education, and systems of innovation provide insight into the successes and failures of select knowledge regions. The authors find that areas with a solid industrial base benefit from, but do not necessarily require, formal technology incubation mechanisms to evolve into successful innovation poles. In contrast, remote regions with good research capacity, and those with an average industrial or research base, must develop an entrepreneurial culture and close cooperation between universities, industry and government with formal incubation mechanisms serving as focal points. Scholars of innovation systems, technology policy, entrepreneurship and regional development will find this fascinating study of great interest, as will science and technology policymakers, university officials and regional leaders.