The goal of this thesis is to develop a computer-based lighting simulation framework capable of predicting human non-visual responses to light and to validate novel guidelines that can inform designers about how lighting might affect human non-visual responses in the built environment. The framework consists of four steps, including a mathematical model that accounts for spectral and dynamic variations in light exposure. As a part of the framework, different light exposure patterns are generated to simulate the effects of occupants’ actions, movements, and activities. The results are interpreted based on pre-defined design goals. Light is one of the most significant factors that affect human health and wellbeing in the built environment. Since 2002, when the first reports on the discovery of a novel type of photoreceptor were published, a new field of study started to emerge at the intersection of photobiology and architecture. The novel photoreceptors are the primary mediators of non-visual responses to light in humans, including synchronizing circadian rhythms and directly alerting the brain. These new findings emanating from the photobiology field have sparked a growing interest in the role of lighting design on human health and wellbeing. The novel photoreceptors contain the photopigment meanopsin. Melanopsin is more sensitive to short- wavelength light, with a peak sensitivity that is blue-shifted (λmax ≅ 480 nm), relative to the photopic visual system (λmax ≅ 555 nm), which is dominated by the response of cone photoreceptors. In addition to the difference between the photoreceptors’ spectral sensitivity, researchers have identified intensity, duration/pattern, history, and timing of light exposure as important variables that control the non-visual light response in humans. Considering the blue-shifted sensitivity of the melanopsin-containing photoreceptors, the current recommendations for lighting, which are based mainly on visual criteria, may not provide the necessary amount of light to synchronize important physiological and behavioral rhythms to the 24-hour day. Moreover, a number of recent studies have demonstrated that exposure to bright light can improve alertness, performance, and mood. However, exposures to light at night can disturb circadian rhythms, such as hormone production and sleep-wake cycles, and have been linked to increased risk of cancer. Lighting simulation software tools are designed to evaluate visual requirements and comfort taking into account the stochastic fluctuations linked to the climate and to the behavior of the buildings’ occupants. The evaluation compares simulated light intensity values on a horizontal plane with static threshold values. Since the non-visual system responds slowly to light exposure and adapts to changes in light intensity and spectral composition over much longer time periods than the visual system, the lighting simulation software tools cannot be applied directly to evaluate the non-visual response to light. The response must be evaluated based on dynamic threshold values, which depend on intensity, spectrum, duration, history, and timing of light exposure. Currently, there is no mathematical model that incorporates all five variables to predict the non-visual effects of light on humans. Further, the movements of humans must be simulated to account for the amount of light received at the eye. Thus horizontal sensors on a plane must be replaced with vertical sensors at the eye level that can rotate and move around. The importance of building simulations is growing with increasing complexity of building design and higher performance requirements regarding sustainability. New methods, created at the interface between photobiology and architecture, predicting the non-visual response to light are needed to support design decisions.