During recent decades, through theoretical considerations and analyses of observations and model simulations, the scientific community has fundamentally advanced our understanding of the coupled climate system, thereby establishing that humans affect the Earth's climate. Resulting from this remarkable accomplishment, the COP21 agreement marks a historic turning point for climate research by calling for actionable regional climate change information on time scales from seasonal to centuries for the benefit of humanity, as well as living and nonliving elements of the Earth environment. Out of the underlying United National Framework Convention on climate Change process, improving seamless regional climate forecast capabilities emerges as a key challenge for the international research community. Addressing it requires a multiscale approach to climate predictions. Here we offer a vision that emphasizes enhanced scientific understanding of regional to local climate processes as the foundation for progress. The scientific challenge is extreme due to the rich complexity of interactions and feedbacks between regional and global processes, each of which affects the global climate trajectory. To gain the necessary scientific insight and to turn it into actionable climate information require technical development, international coordination, and a close interaction between the science and stakeholder communities.