This chapter begins with a discussion of the core proteins and intracellular signaling pathways that are associated with the cellular stress response. It outlines the fundamental principles of tissue optics that govern THz skin interactions, including a discussion of the optical properties of skin at THz frequencies. THz spectroscopy and imaging technologies are finding widespread use in biomedical, medical, military, and defense applications. The chapter also provides an overview of the history and the practical uses for these technologies. It discusses photothermal mechanisms and the thermal effects associated with each temperature damage zone. The chapter provides an overview of the cellular processes that are typically activated in cells exposed to environmental stressors, such as heat or THz radiation. THz irradiation of human skin can cause thermal gradients that result in appreciable increases in tissue temperature. The chapter concludes with recent data, which suggests that human cells express a signature gene expression profile when exposed to THz radiation.