Low-level light therapy (LLLT) using red to near-infrared (NIR) (630–1000 nm) light has gained attention in recent years as a therapy in ophthalmology, neurology, dermatology, dentology, and regenerative medicine. Advancement in the basic science fields of photobiology has propelled LLLT into the therapeutic revolution. The potential mechanisms on LLLT-induced biological effects have been investigated by numerous researchers throughout the world. This article reviews the current intracellular signaling cascades in photobiology and photomedicine under the influence of red to NIR light on mammalian cells. Specifically, mitochondrial retrograde signaling initiated by cytochrome c oxidase photomodulation is discussed in detail in the treatment of indications using LLLT, such as vitiligo management, retinal protection, and tumor therapy. The pathways through activating receptor tyrosine kinases are also highlighted in LLLT-induced neuroprotection, wound healing, and skeletal muscle regeneration. The understanding of the LLLT-induced biological reactions in cellular and subcellular levels is crucial for the advancement of LLLT in treatment of diseases.