After the Greek Independence (1830), the first King, Otto from the Wittelsbach dynasty (Bayer), was married to Amelia from the House of Oldenburg (1836). Their failure to produce an heir to the throne, eagerly expected by the people, contributed much to their abdication in 1862, as an additional factor at the general, opposition to their way of governing. The responsibility for the couples sterility became a matter of political controversies among their families, their countries and the other European thrones after the unsuccessful medical diagnoses and treatments of the most eminent Greek and German physicians. This paper examines their failure to continue the throne, the medical circumstances, and the historical and political consequences.