The discovery of a novel non-rod, non-cone photoreceptor in the human eye that mediates a number of effects on the brain has sparked a growing interest in incorporating these non-visual effects of light into the design process of buildings. Appropriately–timed light exposure has the potential to stabilize and improve circadian rhythms, including sleep, and has direct stimulating effects on alertness and performance. The novel photoreceptors are more sensitive to blue light than the rods and cones used for vision, and respond differently to light intensity, duration, history and timing of a light exposure. The dynamic behavior of the non–visual system provides new challenges in evaluating lighting performance of buildings. In this proof–of–concept study, a novel model that predicts the non–visual responses to light is introduced. The model is used as a part of simulation–based framework for the evaluation of daylighting performance. The evaluation includes four different light pattern generation methods used to investigate the influence of occupants’ movements and activities on simulation results. The framework is applied to the re–design of a healthcare facility. The results lead to new ideas and suggestions for future re–design.