Myocardial fibrosis is recognized as the pathologic entity of extracellular matrix remodeling. Diffuse, reactive fibrosis is being increasingly recognized in a variety of conditions despite the absence of ischemia. Regardless of the etiology, fibrosis leads to increased myocardial stiffness thereby promoting cardiac dysfunction. This may present clinically with symptoms of cardiac failure although often this is a subclinical disease. Various imaging modalities and collagen biomarkers have been used as surrogate markers to assess the presence, extent, and turnover of myocardial fibrosis. Techniques using echocardiography, cardiac magnetic resonance, and nuclear imaging have been developed to detect early features of systolic and diastolic left ventricular dysfunction and impaired contractile reserve. Further identification of diffuse reactive fibrosis may be possible with evolving cardiac magnetic resonance and molecular techniques. The goal of these approaches is to enable targeted therapy to be instituted earlier, leading to prevention of disease progression and fibrosis accumulation long term.