The heart consists of a multitude of diverse cardiomyocyte cell types, including atrial, ventricular and pacemaker cells, which cooperate to ensure proper cardiac function and circulation throughout the body. The rhythm of the heart beat is regulated by the sinoatrial node (SAN), functionally known as the cardiac pacemaker. Loss or dysfunction of these pacemaker cardiomyocytes leads to severe cardiac arrhythmias, syncope and/or even death. Although artificial pacemakers exist to help overcome these issues, several serious limitations and problems have emerged with this approach over the past several decades including electrode fracture or damage to insulation, infection, re-operations for battery exchange, and venous thrombosis. Moreover, size mismatch and the fact that pacemaker leads do not grow with children are a concerning problem. Thus, replacing artificial pacemakers with biological pacemakers potentially overcomes these artificial pacemaker issues including the expense and complications associated with device replacement, device or lead failure, and infection. To achieve these goals, understanding how pacemaker cardiomyocytes are generated is necessary to develop a human biological pacemaker for cardiac cellular therapies.