Financial sustainability is not a driving force of HealthGrids today, as a previous desk research survey of 22 international HealthGrid projects has showed. The majority of applications are project based, which puts a time limit of funding, but also of goals and objectives. Given this situation, we analysed two initiatives, WISDOM and MammoGrid from an economic, cost-benefit perspective, and evaluated the potential for these initiatives to be brought to market as self-financing, sustainable services. We conclude that the topic of HealthGrids should be pursued further because of the substantial potential for net gains to society at large. The most significant hurdle to sustainability – the discrepancy between social benefits and private incentives – can be solved by sound business models.