Mathematical modeling is of crucial importance for understanding the complexity of biological systems. Where biological experiments educate us about nature itself, mathematical models allow us to make prediction on the outcome of events based on current theories and hypotheses. In the field of cardiology, modeling has an important role in forward and inverse calculations between local cardiac events and the body surface ECG or the understanding complex atrial or ventricular arrhythmias. To develop and optimize an accurate mathematical model experimental data is required. Optical imaging has enabled the recording of epicardial, and also transmural, activation and repolarization patterns with a high spatial resolution. Also, optical imaging allows to relate the metabolic state and ionic homeostasis with cardiac electrophysiology by measuring simultaneously membrane voltage and Ca2+ and Na+ with fluorescent indicators or NADH, which has its own fluorescent spectrum. In this talk I will discuss several optical imaging modalities as they are applied to study human non-failing and failing hearts.