Worldwide, cardiovascular diseases affect millions, cause serious economic burdens, and represent the number one cause of death. A broad range of pathological cardiac conditions is associated with myocardial tissue remodeling and fibrosis. Cardiac fibrosis reflects the exaggerated accumulation of extracellular matrix components, and activation of stromal cell compartments in the tissue, followed by acute or chronic inflammatory responses (see the Figure 1). Progressive cardiac fibrosis has been recognized to cause life-threatening arrhythmias. The development of life-saving therapeutic strategies and new medications requires extensive scientific efforts to understand the pathophysiology of pro-arrhythmogenic fibrosis, which is currently poorly understood. Understanding the cellular and molecular roots of cardiac fibrogenesis is crucial for identifying potential diagnostic and therapeutic targets in cardiovascular diseases. The aim of this Research Topic is a wide-ranging overview of the current understanding of the mechanisms of myocardial fibrosis across diverse cardiovascular disorders and its evaluation in patients.