This chapter describes problems with the traditional view of failure in scientific inquiry and intervention development; the evolution of scientific inquiry, including the value of transdisciplinarity as a unifying approach; how methods of participatory design – especially design-thinking – leverage failure; and example cases using iterative design and initial failures to achieve success. Scholars have identified many reasons why traditional research theory and methods do not align well with understanding or addressing complex problems, and one of these reasons is a lack of attention to failure. In addition to the biological, psychological and societal pressures to avoid dealing with failure, the foundation of scientific inquiry and changes to it over time help explain the origin of traditional research approaches and why the importance of failure has been overlooked until more recently. The scientific approach reflects both perceptions of reality and also ways of seeking knowledge to understand it.