The complex mechanical properties of skin have been studied intensively over the past decades. They are intrinsically linked to the structure of the skin at several length scales, from the macroscopic layers (epidermis, dermis and hypodermis) down to the microstructural organization at the molecular level. Understanding the link between this microscopic organization and the mechanical properties is of significant interest in the cosmetic and medical fields. Nevertheless, it only recently became possible to directly visualize the skin’s microstructure during mechanical assays, carried out on the whole tissue or on isolated layers. These recent observations have provided novel information on the role of structural components of the skin in its mechanical properties, mainly the collagen fibers in the dermis, while the contribution of others, such as elastin fibers, remains elusive. In this chapter we present current methods used to observe skin’s microstructure during a mechanical assay, along with their strengths and limitations, and we review the unique information they provide on the link between structure and function of the skin.