Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by episodic syncope and sudden death. CPVT is caused by abnormal intracellular Ca2+ handling resulting from RYR2 or CASQ2 mutations. Our specific aims: (1) investigate the electrophysiological and Ca2+ handling properties of cardiomyocytes derived from induced pluripotent stem cells (iPSC-CM) generated from CPVT patients carrying mutations in the RYR2 and CASQ2 gene (CPVT1 iPSC-CM, CPVT2 iPSC-CM). (2) Investigate the responsiveness of CPVT1 iPSC-CM and CPVT2 iPSC-CM to ?-adrenergic stimulation and antiarrhythmic drugs. Our major findings: (1) Isoproterenol generated arrhythmogenic delayed afterdepolarizations (DADs) and triggered arrhythmias in the mutated but not in the healthy iPSC-CM. Importantly, in the mutated cardiomyocytes isoproterenol also caused oscillatory pre-potentials which are arrhythmogenic late diastolic depolarizations. (2) The DADs were abolished by the ?-blocker bisoproplol. (3) Isoproterenol generated triggered beats and increased diastolic Ca2+ levels in CPVT1 iPSC-CM and CPVT2 iPSC-CM. In conclusion, our results demonstrate that iPSC-CM constitute a superb model for investigating the arrhythmogenic phenotype and mechanisms underlying inherited arrhythmias, and for drug screening.