Fig. 1. Hierarchical modeling of human breast function. Similarities between the organization of human and mouse mammary glands have enabled observations in one tissue to be transferred to the other. This dynamic exchange of information has led to the gradual development of mammary gland models that now represent a continuum of organotypic systems ranging in complexity from monotypic 3D cultures to multicellular co-cultures to in vivo xenograft models. Each of the 3D models depicted here represents a physiologically relevant assay in its own right. However, when engineered with common cellular components and used in series, these models become invaluable tools for the identification and verification of disease-related molecules as well as for the design and translation of effective drug therapies. Future in vivo models that are more faithful to the human mammary microenvironment may be achieved in a `humanized' mouse model in which mammary glands are entirely repopulated by breast cell types of human origin. Ep, epithelial cell; Myoep, myoepithelial cell. Adapted from previous publications (Ronnov-Jessen et al., 1996; Schmeichel et al., 1998).