BACKGROUND: The introduction of chronotherapy (that is improving a drugs therapeutic efficacy by paralleling the drugs plasma levels to circadian rhythms) has recently become a focus of interest. OBJECTIVE: This article addresses the efficacy and potential shortcomings of chronotherapy, and focuses on one specific type of chronotherapy: a novel long-acting diltiazem formulation, DTZ-LA. METHODS: We reviewed the literature to assess the clinical benefits and shortcomings associated with DTZ-LA in the management of hypertension and angina. RESULTS/CONCLUSIONS: The clinical benefits of DTZ-LA outweigh its disadvantages when surrogate outcomes are evaluated, but it still remains to be determined whether chronotherapy benefits hard clinical outcomes. Nonetheless, chronotherapy has the potential to address the cardiovascular triggers that peak in the early morning hours when the preponderance of cardiovascular events occur, as well as providing better target organ protection compared with non-chronotherapeutic therapy.