Humans are continuously exposed to a variety of carcinogenic and mutagenic stimuli, including environmental toxins, radiation and viral as well as other infections. Tumor metastasis is responsible for approximately 9% of all cancer-related deaths. The tumor microenvironment (TME) contains many distinct cell types, including endothelial cells and their precursors, pericytes, smooth muscle cells, fibroblasts, carcinoma-associated fibroblasts, myofibroblasts, neutrophils, eosinophils, basophils, mast cells, T and B lymphocytes, natural killer cells and antigen presenting cells (APC) such as macrophages and dendritic cells. Recent evidence has shown that stromal tissue is much more than a passive bystander in the development and progression of cancers. The clinical therapy for many types of human cancers has mainly focused on the malignant cancer cell itself, and have made great achievements, yet cancer therapy still remain a great challenge. This review highlights the evidence for the crucial role of the tumor microenvironment in tumor progression and metastasis.