The circadian clock, a highly specialized, hierarchical network of biological pacemakers, directs and maintains proper rhythms in endocrine and metabolic pathways required for organism homeostasis. The clock adapts to environmental changes, specifically daily light-dark cycles, as well as rhythmic food intake. Nutritional challenges reprogram the clock, while time-specific food intake has been shown to have profound consequences on physiology. Importantly, a critical role in the clock-nutrition interplay appears to be played by the microbiota. The circadian clock appears to operate as a critical interface between nutrition and homeostasis, calling for more attention on the beneficial effects of chrono-nutrition.