Skin pigmentation is regulated by interactions between melanocytes and neighboring cells, such as keratinocytes, fibroblasts or inflammatory cells. Up- or downregulation of paracrine factors secreted from these cells control melanocyte functions and cause pigmentary changes. Several clinical examples underline the importance of dermal factors in the control of epidermal pigmentation. Human dermal fibroblasts secrete several paracrine factors including stem cell factor (SCF), keratinocyte growth factor (KGF), Wnt inhibitory factor 1 (WIF-1), neureguln-1, Dickkopt-related protein 1 (DKK1), and pleiotrophin. The fibroblast activity is regulated by extrinsic factors such as ultraviolet radiation. Understanding of the roles of proteins secreted from neighboring skin cells in the function of melanocytes may provide valuable information regarding the development of target proteins for treatment and a better understanding of the pathophysiology of cutaneous pigmentation.