Steroid hormones coordinate and control the development and function of many organs and are implicated in many pathological processes. Progesterone signaling, in particular, is essential for several important female reproductive functions. Physiological effects of progesterone are mediated by its cognate receptor, expressed in a subset of cells in target tissues. Experimental evidence has accumulated that progesterone acts through both cell intrinsic as well as paracrine signaling mechanisms. By relegating the hormonal stimulus to paracrine signaling cascades the systemic signal gets amplified locally and signaling reaches different cell types that are devoid of hormone receptors. Interestingly, distinct biological responses to progesterone in different target tissues rely on several tissue-specific and some common paracrine factors that coordinate biological responses in different cell types. Evidence is forthcoming that the intercellular signaling pathways that control development and physiological functions are important in tumorigenesis. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.