Much of the conflict took place during the long regency of Queen Catherine de' Medici, widow of Henry II of France, for her minor sons. It also involved a dynastic power struggle between powerful noble families in the line for succession to the French throne: the wealthy, ambitious, and fervently Roman Catholic ducal House of Guise (a cadet branch of the House of Lorraine, who claimed descent from Charlemagne) and their ally Anne de Montmorency, Constable of France (i.e., commander in chief of the French armed forces) versus the less wealthy House of Condé (a branch of the House of Bourbon), princes of the blood in the line of succession to the throne who were sympathetic to Calvinism. Foreign allies provided financing and other assistance to both sides, with Habsburg Spain and the Duchy of Savoy supporting the Guises, and England supporting the Protestant side led by the Condés and by the Protestant Jeanne d'Albret, wife of Antoine de Bourbon, King of Navarre, and her son, Henry of Navarre.
Moderates, primarily associated with the French Valois monarchy and its advisers, tried to balance the situation and avoid open bloodshed. This group (pejoratively known as Politiques) put their hopes in the ability of a strong centralized government to maintain order and harmony. In contrast to the previous hardline policies of Henri II and his father Francis I, they began introducing gradual concessions to Huguenots. A most notable moderate, at least initially, was the queen mother, Catherine de' Medici. Catherine, however, later hardened her stance and, at the time of the St. Bartholomew's Day massacre in 1572, sided with the Guises. This pivotal historical event involved a complete breakdown of state control resulting in series of riots and massacres in which Catholic mobs killed between 5,000 and 30,000 Protestants over a period of weeks throughout the entire kingdom.
At the conclusion of the conflict in 1598, the Protestant Henry of Navarre, heir to the French throne, converted to Catholicism and was crowned Henry IV of France. He issued the Edict of Nantes, which granted Huguenots substantial rights and freedoms though this did not end Catholic hostility towards them or towards him, personally. The wars of religion threatened the authority of the monarchy, already fragile under the rule of Catherine's three sons and the last Valois kings: Francis II, Charles IX, and Henry III. This changed under the reign of their Bourbon successor Henry IV. The edict of Nantes was revoked later in 1685 with the Edict of Fontainebleau by Louis XIV of France. Henry IV's wise governance and selection of able administrators did leave a legacy of a strong centralized government, stability, and economic prosperity that has gained him the reputation as France's best and most beloved monarch, earning him the designation "Good King Henry".
Along with French Wars of Religion and Huguenot Wars, the wars have also been variously described as the "Eight Wars of Religion", or simply the "Wars of Religion" (only within France).
The exact number of wars and their respective dates are subject to continued debate by historians: some assert that the Edict of Nantes in 1598 concluded the wars, while the ensuing resurgence of rebellious activity leads some to believe the Peace of Alais in 1629 is the actual conclusion. However, the agreed upon beginning of the wars is the Massacre of Vassy in 1562, and the Edict of Nantes at least ended this series of conflicts. During this time, complex diplomatic negotiations and agreements of peace were followed by renewed conflict and power struggles.