Encountering patients with Fabry disease promptly reveals the complexity of this condition. Similar to other hereditary progressive diseases multiple factors beginning from a first pathogenic substrate may result in a multi-systemic manifestation. We found ourselves still far from having understood all processes leading to the various clinical picture of this disease. Starting with the accumulation of Globotriaosylceramide (Gb3) since birth and a subsequent progressive endothelial dysfunction Fabry disease manifests itself in later stages with multiple organ involvement–disease associated cardiopathy being the main determinant for morbidity and prognosis. Besides the traditional notion of left ventricular hypertrophy and replacement fibrosis, specific electrocardiographic changes and signs have been shown by our analyses to useful in early recognition and staging of patients with suspected cardiac involvement. Of note, these parameters often occur before macroscopic cardiac structural changes are detected and may be of importance for an early establishment of enzyme replacement therapy.