History in the making
The British Empire's period of global domination included the reign of Queen Victoria, but by then most real power had already transitioned from the monarch to the Prime Minister. Moving further back in history, the Spanish, Ottoman, Umayyad/Abbasid, Roman, and Persian Empires never had female rulers during their periods of pre-eminence. Before that, the world was too politically fragmented to speak meaningfully of any one state, and therefore its leader, as being the most powerful globally.
Hillary will be the first. I have a feeling she'll be far from the last.