Human skin exhibits exquisite site-specific morphologies and functions. How are these site-specific differences specified during development, maintained in adult homeostasis, and potentially perturbed by disease processes? Here, we review progress in understanding the anatomic patterning of fibroblasts, a major constituent cell type of the dermis and key participant in epithelial-mesenchymal interactions. The gene expression programs of human fibroblasts largely reflect the superimposition of three gene expression profiles that demarcate the fibroblast's position relative to three developmental axes. The HOX family of homeodomain transcription factors is implicated in specifying site-specific transcriptional programs. The use of gene, tiling, and tissue microarrays together gives a comprehensive view of the gene regulation involved in patterning the skin.