Cancer is generally viewed as the result of disrupted intra-and intercellular homeostatic regulation. Once the homeostatic balance is lost and malignant transformation has occurred, microenvironmental factors such as degradation of matrix components and host-tumor interactions are essential for survival and growth of malignant cells. Within the previous year, cadherins and matrixins (matrix metalloproteinases) have emerged as key factors in these processes. The pathways involved are interconnected and detailed knowledge about the biologic significance of each member in a given pathway is essential for our understanding of oncogenesis. Restoration of E-cadherin-mediated control over melanoma cells and modulation of the involved regulation pathways are promising novel therapeutic strategies. Another approach is the rational design of inhibitors that perturb matrix metalloproteinases in a particular cell type and interrupt tumor-specific proteinase activation cascades. Advances in these fields will lead to the development of better tools for prevention, diagnosis, and therapy.