The physical character of the skin, the tough dry exterior, signifies its major function, that of protection from the environment. Less obvious is the complex cellular environment, which provides a site for interaction between the tissue and such physical assaults as heat, hydration and light, the object of which is to maintain an internal physiological homeostasis. It is remarkable that despite wide variations in environmental conditions, the skin has the capacity to maintain a stable microbial ecosystem. It is the purpose of this chapter to assess the importance of physical factors, in the skin and from the environment, in maintaining normal microbial colonization and in changes resulting in infection. Previous reviews have provided insight into the importance of skin structure, hydration, temperature, pH, oxygen and carbon dioxide gradients. Much has been learned of other physical properties of the skin, such as optical, electrical and mechanical properties, but their relationship to microbial colonization has received less attention. Hydrophobicity is of importance for adherence, yet its relationship to colonization of the skin surface and microbial invasion is poorly understood. Thus, knowledge of the biophysical properties of the skin in relation to microbial colonization has lagged behind progress in other areas, and many of these aspects present challenges for future investigation. Microbial colonization of the skin will be discussed in relation to the skin structure, pH, temperature, hydration, oxygen and carbon dioxide, and light. The physical factors involved in adherence will also be reviewed.