There is an enormous amount of intricate research available on specific aspects of building performance in relation to users. However, there is currently no framework for designers to bring together these diverse findings. As a result, a significant opportunity is being missed to support radically more positive outcomes for the occupants of buildings. To help address this gap, this article proposes a framework that captures the essence of an individual’s holistic experience of spaces, created by the combined impacts received through their senses and mediated by their brain. The early sections illustrate the complex and dynamic ways in which humans receive information about their surroundings through their senses, with profound, but fragile and interactive effects on human health, mood and performance. This is strategically framed using neuroscience theories about the way the human brain makes calculations to link perceptions to actions. This leads to the proposition that design should take into account issues of naturalness, individualization and level of stimulation. It is further suggested that a multidisciplinary, multi-level research approach is needed to support the creation of spaces that provide people with sensory environments that help them reach, or sustain, their fullest possible potential.