||Fibrillation is defined as turbulent cardiac electrical activity and results in the inability of the myocardium to contract. When fibrillation occurs in the ventricles, it is known as ventricular fibrillation (VF). The consequence of VF is sudden death unless treated immediately. Fibrillation can also occur in the atria and is known as atrial fibrillation (AF). The consequences of atrial fibrillation (AF) are less immediate; however, it leads to increased risk of stroke. Despite the impact of fibrillatory arrhythmias, there are many gaps in our mechanistic knowledge of these arrhythmias. The purpose of this dissertation is to study through several projects how different cardiac substrates help initiate and/or sustain fibrillation. The first project examined several properties of the ventricular conduction system during VF. The conduction system coordinates excitation and consequently coordinates the contraction of the ventricles. Despite the conduction system's unique structure, its role in VF remains unclear. We examined the proximal conduction system and found that it develops a more rapid activation rate than the ventricular myocardium during prolonged VF, and may be driving the arrhythmia. The second and third projects examined the effects of fibrosis on electrical conduction to initiate and/or sustain AF. Despite fibrosis being associated with AF, it is still unknown whether it is a byproduct of an underlying heart disease and does not in itself promote AF, or if it affects the organization of conduction during fibrillation to promote AF. In the second project we studied the effect of fibrosis on conduction following different types of triggers. We found that fibrosis causes transverse conduction slowing following premature stimulation, which makes AF more likely to initiate. As AF persists, single episodes of AF last longer before the patient transitions into normal sinus rhythm, and in some cases AF can become permanent. The third project examined why some patients may never transition from AF to normal sinus rhythm. Specifically, this project found that regions of dense fibrosis anchor high-frequency activation that may be driving the arrhythmia. These studies showed that fibrosis causes conduction changes that make AF more likely to initiate and to be sustained.