This is a very long period of time, in which a great many changes took place. The earlier part of it was filled with upheavals in European society which are sometimes collectively known as "the Crisis of the Late Middle Ages." These include the Great Famine of 1315–1317 and the Black Death of 1347–1351. The latter event was particularly destructive, and may have killed up to 200 million people. It took more than a century for Europe to regain the population levels that had prevailed before the Black Death.
Apart from the deadliest pandemic in recorded history, the two most major types of challenge for late-medieval and early-modern Europe were frequent wars and uprisings and a schism in the Church. Perhaps the most notable war was the Hundred Years War, which actually lasted for 116 years, between 1337 and 1453. This was really a series of wars, and included a peasant's revolt in 1358. A similar peasant uprising took place in England in 1381.
Further unrest was caused by religious schism, which divided Europe at the end of the fourteenth century when two, and eventually three, men claimed the papacy. This was only a prelude to the more permanent schism at the beginning of the sixteenth century, when Martin Luther's breach with the papacy created the division between the Catholic Church in Southern Europe and the Protestant churches of the North.