Epithelial-stromal interactions are important not only in growth, development, and functional cytodifferentiation of the prostate but also in derangements of prostate gland such as BPH and prostate carcinoma. This chapter explores the roles of epithelium and stroma during this delicate process and highlights the role and mutual influence of each on the other. It also examines the importance of ECM in mediating the effects of androgens and drawn attention to estrogen and genetic factors in the process. During this process of epithelial-stromal interaction, growth factors play a central role in mediating the interactions. This chapter focuses on the role of several growth factors including epidermal growth factor, fibroblast growth factor, transforming growth factor alpha, transforming growth factor beta, insulin-like growth factor-1, vascular endothelial growth factor, nerve growth factor, platelet-derived growth factor, and hepatocyte growth factor. This chapter emphasizes the importance of epithelial-stromal interactions in tumorigenesis and highlights the switch of paracrine to autocrine mode during the process of carcinogenesis.