The malignant process, transformation of normal cells, proliferation, and metastasis formation, was considered as if originating from one single cell. Although the intrinsic mechanisms of transformation from the normal to the malignant state were both confirmed, an increasing body of evidence points to the surrounding matrix and cell-matrix interactions as major players in this process. Some of the most important arguments in favor of this contention are cited and commented in this chapter. Another important question concerns the relationship between the aging process and malignant transformation. A few decades ago, the frequency of clinically manifest tumors of several organs and tissues appeared to increase with age. As, however, average life expectancy increased rapidly over the last decades, clinical frequency of malignant tumors did not follow this tendency. It was argued that late in life the malignant process appears to decline. This justly inspired several teams to study the relationship between cellular senescence and malignant transformation. This is now an actively growing field which deserves special attention. Some of the pertinent experimental and theoretical arguments in favor of an antioncogene - mediated switch between these two processes are also reviewed with the caveat that this important and new subject of basic and clinical research on the malignant process is just at its beginning. It will certainly take an increasing importance during the coming years and decades with the hope to contribute to answer one of the most burning questions concerning the aging process: will life expectancy continue to increase linearly as predicted by some gerontologists, or will life expectancy level off or even decline as predicted by other epidemiologists. The relationship between cellular senescence and malignant transformation will play in this respect an important role.