Clock genes, circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN), control various circadian rhythms in many biological processes such as physiology and behavior. Clock gene regulates many diseases such as cancer, immunological dysfunction, metabolic syndrome and sleep disorders etc. Dosing time influences the effectiveness and toxicity of many drugs. The pharmacodynamics of medications as well as pharmacokinetics influences chronopharmacological phenomena. For example, abnormal increase in serum retinol levels is detected in mice with 5/6 nephrectomy (5/6Nx), an experimental model of CKD (chronic kidney disease), which is caused by the down-regulation of hepatic expression of Cyp3a11, Cyp26a1, and Dbp through increasing of serum TGF-β1. The elevated retinol levels also induce the activation of caspase and apoptotic cell death in the kidney, further exacerbating the pathologies of CKD. In contrast, 5/6Nx-induced renal inflammation and apoptotic cell death are attenuated in Clock mutant (Clk/Clk) mice even though they exhibit high serum levels of retinol and its binding protein (RBP4). Serum accumulation of retinol induces the CLOCK/BMAL1-mediated transactivation of GPR68 in circulating monocytes, and migration of GPR68-expressing monocytes into the heart ventricle exacerbates inflammation and fibrosis. Overall, clock genes are critical candidates for therapy associated with chronopharmacological strategy of kidney-liver-heart axis via retinol and monocytes as shown by the accumulated data. Therefore, we introduce an overview of chrono-drug discovery and development.