Abstract :The proper functionality of our cells requires a temporal orchestration of many physiological processes. The “art director” of this symphony is represented by the endogenous molecular clock, which is able to activate or repress the expression of more than 10% of human genes in a “crescendo” and “decrescendo” in time with the environment [1]. Being designated to modulate important physiological activities, such as brain functions, pathogen defense and metabolism, it is not surprising that disruption of the molecular clock is associated with a variety of human pathologies [1-5]. Less obvious, but highly fascinating, would be the possibility to modulate the molecular clock to cure a pathology. Recently, we obtained the first prove that the pharmacological modulation of a clock-related protein is a suitable strategy for the identification of innovative anticancer approaches [6]. Although it is wide recognized that cancer cells and normal cells do not share a common clock, the molecular basis of this difference is still unclear. We discovered an unpredicted cancer-specific “paralog switch” of the clock regulatory nuclear receptor, REV-ERB [6].