Our paper aims to re-interpret e-health at the intersection between the fields of Social Innovation (SI) and Knowledge Ecosystems (KE). In doing this, a systematic literary review about SI, KE and e-health was carried on, in order to identify common issues between the two selected fields of research. Taking into account the review results, we identified the notion of co-creation as the most effective in the investigation of e-health at the merging between SI and KE theoretical perspectives. The EMSE (Emergency Medical Service Ecosystem) model was, finally, examined within the provided theoretical framework.