Tissue parenchyma is the functional unit of an organ and all of the remaining cells within that organ collectively make up the tissue stroma. The stroma includes fibroblasts, endothelial cells, immune cells, and nerves. Interactions between stromal and epithelial cells are essential for tissue development and healing after injury. These interactions are governed by growth factors, inflammatory cytokines and hormone signaling cascades. The steroid receptor coactivator (SRC) family of proteins includes 3 transcriptional coactivators that facilitate the assembly of multi-protein complexes to induce gene expression in response to activation of many cellular transcription factor signaling cascades. They are ubiquitously expressed and are especially critical for the developmental function of steroid hormone responsive tissues. The SRCs are overexpressed in multiple cancers including breast, ovarian, prostate and endometrial cancers. In this review, we focus on the role of the SRCs in regulating the functions of stromal cell components responsible for angiogenesis, inflammation and cell differentiation.