Skin is the largest organ of human body that acts as the interface between the internal tissues of the body and the external environment to provide barrier function and protection. Clothing, called 'the second skin', covers most parts of the body, most of time, in majority of the places not only providing additional shield for the body but also creating a portable living microclimate for its survival. However, how the skin and 'the second skin' interact with each other to serve the protective and biological functions is indeed a mystery and a scientific understanding of the phenomenon is still in its infancy. The aim of this research is to fill the knowledge gaps and establish a theoretical framework for delineating the effects of clothing on skin physiology.;This aim has been achieved through a systematic study to establish theoretical framework based on a thorough literature review and by undertaking a series of wear trials in mildly cold and hot environmental conditions, as well as under solar exposure. A theoretical framework of effects of clothing on skin physiology was developed by considering the potential mechanisms involved in physics, biochemistry, physiology, neuropsychology and immunology. A set of hypotheses were then proposed to explain the possible physiological interactions between clothing and skin. This theoretical framework and hypotheses were further tested by a series of wear trials conducted in mildly cold and hot environmental conditions as well as under solar exposure.;To reiterate, in this study, the clothing-body interactions in mild cold and hot environments as well as under solar exposure have been investigated. Two comprehensive frameworks have been developed to describe the mechanisms of the ways in which physical properties of fabric influence skin physiology, thermophysiology and neuropsychology. The outcomes of this research should contribute towards developing a scientific understanding on how clothing affects skin physiological health, comfort and protection of the body under different environmental conditions.