It is now widely accepted that the tumor microenvironment is a pathologically active niche that shapes tumor nature, evolution and response to treatment. Close interactions between cancer cells and stroma are known to regulate several cancer pathways and thus the determination of different tumor-stromal interactions could be an important step in invasiveness. The breast cancer microenvironment is a complex combination of several different cell types and molecules and a key contributor to tumor development and progression. The microenvironment includes fibroblasts, macrophages, immune cells, tumor-infiltrating lymphocytes, endothelial cells and angiogenic vascular cells, whereas stromal cells surround and interact with tumor cells. Recent data demonstrate significant gene expression alterations in microenvironment cells during disease progression and several stromal cell types are implicated in promoting the "hallmarks of cancer", which can be explored as targets for cancer therapy. Besides identifying new therapeutic targets, the microenvironment has also been implicated in chemotherapy resistance, suggesting that the crosstalk between cancer and its microenvironment is a promising strategy to target breast cancer.