Computational modelling and simulation of penetration processes in the skin barrier on multiple biological scales in space and time is increasingly being recognized as a powerful tool to develop and to refine hypotheses, focus experiments, and enable more accurate predictions. One area of the ongoing research effort is physiologybased transport models. On the one hand, these are based on first principles and describe processes in the skin mathematically in terms of conservation equations. On the other hand, these models employ detailed morphology information and are thus capable of exploiting relationships between form and function. Particularly, such models provide an understanding how microscopic physiological structure and heterogeneity govern penetration. In this chapter, we describe microscopic geometry models of the skin cells (e.g. corneocytes) and the lipid bilayers of the stratum corneum (SC).