Genetically or surgically altered mice are commonly used as models of human cardiovascular diseases. Electrocardiography (ECG) is the gold standard to assess cardiac electrophysiology as well as to identify cardiac phenotypes and responses to pharmacological and surgical interventions. A variety of methods are used for mouse ECG acquisition under diverse conditions, making it difficult to compare different results. Non-invasive techniques allow only short-term data acquisition and are prone to stress or anesthesia related changes in cardiac activity. Telemetry offers continuous long-term acquisition of ECG data in conscious freely moving mice in their home cage environment. Additionally, it allows acquiring data 24/7 during different activities, can be combined with different challenges and most telemetry systems collect additional physiological parameters simultaneously. However, telemetry transmitters require surgical implantation, the equipment for data acquisition is relatively expensive and analysis of the vast number of ECG data is challenging and time-consuming. This review highlights the limits of non-invasive methods with respect to telemetry. In particular, primary screening using non-invasive methods can give a first hint; however, subtle cardiac phenotypes might be masked or compensated due to anesthesia and stress during these procedures. In addition, we detail the key differences between the mouse and human ECG. It is crucial to consider these differences when analyzing ECG data in order to properly translate the insights gained from murine models to human conditions.