Well-being in the built environment is a topic that features frequently in building standards and certification schemes, in scholarly articles and in the general press. However, despite this surge in attention, there are still many questions on how to effectively design, measure, and nurture well-being in the built environment. Bringing together experts from academia and the building industry, this paper aims to demonstrate that the promotion of well-being requires a departure from conventional agendas. The ten questions and answers have been arranged to offer a range of perspectives on the principles and strategies that can better sustain the consideration of well-being in the design and operation of the built environment. Placing a specific focus on some of the key physical factors (e.g., light, temperature, sound, and air quality) of indoor environmental quality (IEQ) that strongly influence occupant perception of built spaces, attention is also given to the value of multi-sensory variability, to how to monitor and communicate well-being outcomes in support of organizational and operational strategies, and to future research needs and their translation into building practice and standards. Seen as a whole, a new framework emerges, accentuating the integration of diverse new competencies required to support the design and operation of built environments that respond to the multifaceted physical, physiological, and psychological needs of their occupants.