Building a culture of prevention presents many challenges, all of which originate from and refer back to both strengths and weaknesses of this effort. In this invited commentary, I provide an overview of these challenges and remaining open questions extracted from the original contribution enclosed in the special issue. Crucial questions that need to be addressed are the use of formal models of a "culture of prevention"; how the interplay of local values, alliances, and co-creational processes can be reflected in other experiences; and evaluation of the culture change itself.
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