Two-sided markets arise in situations in which there are externalities and in which transaction costs, broadly considered, prevent the two sides from solving this externality directly. In the e-health market, the expansion of the Internet economy has shown to be significant in stimulating the entry of business organizations, many of which are already in two-sided markets.An e-health two-sided market needs to offer sustainable structures, i.e., an ecosystem to support a flexible model that must meet unexpected demand and at the same time be able to handle high demand peaks and long periods if needed. In this chapter we introduce key concepts and factors that are of relevance in two-sided markets. We further discuss the fundamental role of two-side market ecosystem in enabling parties to realize gains from trade or other interactions by reducing the transactions costs of finding each other and interacting. Hence, e-health market ecosystems first and foremost need to be designed for adaptability and network effects. We discuss issues that influence the sustainability and further development of a two-sided e-health market.