As the technology of computer-assisted ECG analysis continues to advance the frontier of multi-lead acquisition and real time analysis, conceptual approaches to the research applications as well as to the electrical and clinical validity of changes in the ECG signal amongst heterogeneous patient groups need to be continually reassessed. Comparisons between different devices, lead configurations, rates of acquisition, approaches to analysis, and patient populations may have large gaps that will require cautious extrapolation and careful investigation.