Rapid urbanization presents one of the most urgent challenges of our times. Cities must cope with poor air quality, heat island effects, increased flood risk and the frequency/severity of extreme events (e.g., droughts and heat waves), increasing crime and social inequity, poverty and degraded urban environments, amongst other negative consequences. Climate change adaptation and mitigation as well as sustainable management are therefore key challenges for cities in Europe and around the world. What must be developed therefore is a robust, wide evidence-base and reference framework of nature-based solutions (NBS) - measures that mimic the complex features and processes of natural ecosystems - for local/regional city authorities and other policy and decision makers to increase climate resilience and address inclusive urban regeneration in cities. In response to this need, we propose an applicative framework for NBS using the structure of the DPSIR (Driving force-Pressure-State-Impact-Response) model, in conformity with European Community standards. Indeed, under the umbrella of the EC's Framework Program - Horizon 2020 - international institutions, scientific experts and policy makers worldwide are seeking to increase collaboration with cities to enhance ecosystem services and develop the evidence-base for the economic, social and environmental benefits of nature-based solutions. They are eager to exchange knowledge and inspire positive action for nature in urban areas to meet their growing social and environmental challenges. The time has come to acknowledge NBS as the most fitting response to the numerous challenges posed by our changing climate and for the realization of sustainable and healthy cities. It is hoped that this article will pioneer others in settling the issue for NBS as the undisputable answer to challenged urban landscapes and societies globally.