In an integrated approach, the authors examine the most efficient combination of noninvasive and invasive biochemical, immunologic, functional, molecular, imaging and biopsy-derived biomarkers for their applicability in the diagnosis of cardiomyopathies in general and dilated cardiomyopathy (DCM) in particular. A careful selection out of the cascade of available biomarkers will allow, in individual patients, to diagnose certain conditions of cardiomyopathies without endomyocardial biopsy, e.g., borreliosis, rickettsiosis, HIV cardiomyopathy. Viral persistence in DCM associated with inflammation will need both noninvasive (echocardiography, cardiovascular magnetic resonance) and invasive biomarkers (polymerase chain reaction for viral persistence or their exclusion in case of autoreactive myocarditis and quantitative immunohistology, both from endomyocardial biopsy).