Cytotoxic chemotherapy drugs damage proliferating cells primarily by interfering with mitosis and we now know the molecular target of most of the drugs in clinical use. Even so, non-specificity of cytotoxic agents is a major drawback and their ability to damage normal as well as malignant cells means that cure with chemotherapy is not often achieved. Various strategies have been adopted to enhance the antitumour effect. These include combining drugs with different mechanisms of action, delivering drug directly to the tumour and overcoming cellular resistance mechanisms. With advances in science, rational drug design is now becoming a reality, and mechanism-driven, targeted anticancer agents are being used alongside conventional cytotoxic chemotherapy. Cancer treatment is therefore increasing in complexity, so the challenge for clinicians and scientists now is to manipulate the various treatment options to maximize benefit and minimize harm for individual patients.