Different tumors have different aberrations in signaling and growth stimulation pathways that drive cancer growth. An understanding of these processes is key to the development of new anticancer agents and to identifying optimal treatment strategies and patient populations suitable for specific therapies. It is becoming clear that certain chemotherapeutic drugs such as docetaxel are not simply inhibitors of mitosis and may interact with these tumorigenic mechanisms at a number of levels. This review describes docetaxel's mechanism of action, and provides a basis for understanding how its antitumor activity can integrate with that of different novel agents. Against this background, key docetaxel-novel agent combinations that are currently under clinical investigation are reviewed. How these strategies can be targeted towards specific patient populations (e.g., HER-2 overexpressing metastatic breast cancer patients) to provide optimal therapy is highlighted.