Light plays a crucial role in affecting the melatonin secretion process, and consequently the sleep–wake cycle. Research has demonstrated that the main characteristics of lighting affecting the so-called circadian rhythms are spectrum, light levels, spatial pattern and temporal pattern (i.e., duration of exposure, timing and previous exposure history). Considering that today people spend most of their time in indoor environments, the light dose they receive strictly depends on the characteristics of the spaces where they live: location and orientation of the building, dimensions of the windows, presence of external obstructions, geometric characteristics of the space, optical properties of walls and furniture. Understanding the interaction mechanism between light and architecture is fundamental to design non-visually comfortable spaces. The goal of the paper is to deepen this complex issue. It is divided into two parts: a brief historical excursus about the relationship between lighting practice and architecture throughout the centuries and a review of the available research works about the topic. The analysis demonstrates that despite the efforts of the research, numerous open questions still remain, and they are mostly due to the lack of a shared and clear method to evaluate the effects of lighting on circadian rhythm regulation.