Australia is an interesting case study of biotechnology ecosystem development. Despite its distance from the US biotechnology superclusters, the country has had high expectations for its potential development into a biotechnology superpower. These expectations have not been met over the last two decades. Despite generous R&D tax incentives and a robust network of public research organizations (PROs), the local biotechnology industry has remained small and weak, without a single ‘big biotech’ emerging. Cluster analysis over 11 years of all private and public DBFs indicated that the PRO network output failed to translate to the development by the local biotech industry of drug candidates that could attract Big Pharma deals. Analysis of the investor returns over 15 years from all public drug development biotech firms (DDBs) showed that not a single firm produced attractive long-term investor returns and the sector overall generated negative returns for investors. Despite high promissory expectations, favorable government policies and an inflated view of the quality of the country’s science output, Australia has failed to create a sustainable biotechnology ecosystem. Some of the reasons are identified and suggestions are offered for changes in government policy that could improve value creation by the local biotech sector.