In medical oncology, targeted therapy has emerged over the last decade, as the most promising strategy to fight cancer. In addition, a more complete understanding of tumor heterogeneity and pharmacology of the more conventional anti-cancer agents has led to development of metronomic chemotherapy (MC) (i.e. a more frequent administration of anticancer agents at lower doses then the usual maximally tolerated dose because it has been realized that time of exposure to an effective drug concentration is more important than simply the dose/m2 or kg.), Here, we discuss the nature of the specificity of targeted anti-cancer treatments and conclude that optimizing the schedule is an effective way to improve treatment selectivity.