Since 2009, there have been several profound transformations of the Colombian National System of Science, Technology and Innovation, such as a new law for science, technology and innovation (STI) and a new STI fund, whose resources come from royalties from the exploitation of non-renewable natural resources. These changes present opportunities, challenges and threats to Colciencias, the Colombian government agency in charge of research and innovation funding and promotion. Certainly, the 10 per cent of royalties for STI activities and the creation of iNNpulsa – a new government agency promoting innovation and entrepreneurship – can be seen as both opportunities and threats. The royalties certainly are a major driver of change, since they have come with new rules and funding mechanisms, and these resources are much greater than Colciencias’s budget. Many questions arise: Will the governance of Colciencias and the system be affected? How? Will Colciencias be able to learn from the past, or will it fail to adapt to new circumstances? This chapter tries to answer these questions after presenting the governance practices developed by Colciencias over its 45 years of existence.