One notable exception involved the relationship between the Pope and the Byzantine Emperor. Papal agents, called apocrisiarii, were permanently resident in Constantinople. After the 8th century, however, conflicts between the Pope and the Emperor (such as the Iconoclastic controversy) led to the breaking down of these close ties.

Modern diplomacy's origins are often traced to the states of Northern Italy in the early Renaissance, with the first embassies being established in the thirteenth century. Milan played a leading role, especially under Francesco Sforza who established permanent embassies to the other cities states of Northern Italy. It was in Italy that many of the traditions of modern diplomacy began, such as the presentation of an ambassador's credentials to the head of state.

The practice spread from Italy to the other European powers. Milan was the first to send a representative to the court of France in 1455. Milan however refused to host French representatives fearing espionage and possible intervention in internal affairs. As foreign powers such as France and Spain became increasingly involved in Italian politics the need to accept emissaries was recognized. Soon all the major European powers were exchanging representatives. Spain was the first to send a permanent representative when it appointed an ambassador to the Court of England in 1487. By the late 16th century, permanent missions became the standard.

Many of the conventions of modern diplomacy developed during this period. The top rank of representatives was an ambassador. An ambassador at this time was almost always a nobleman -  the rank of the noble varied with the prestige of the country he was posted to. Defining standards emerged for ambassadors, requiring that they have large residences, host lavish parties, and play an important role in the court life of the host nation. In Rome, the most important post for Catholic ambassadors, the French and Spanish representatives sometimes maintained a retinue of up to a hundred people. Even in smaller posts, ambassadors could be very expensive. Smaller states would send and receive envoys who were one level below an ambassador.

Ambassadors from each state were ranked by complex codes of precedence that were much disputed. States were normally ranked by the title of the sovereign; for Catholic nations the emissary from the Vatican was paramount, then those from the kingdoms, then those from duchies and principalities. Representatives from republics were considered the lowest envoys.

Ambassadors at that time were nobles with little foreign or diplomatic experience and needed to be supported by a large embassy staff. These professionals were sent on longer assignments and were far  more knowledgeable about the  host country. Embassy staff consisted of a wide range of employees, including some dedicated to espionage. The need for skilled individuals to staff embassies was met by the graduates of universities, and this led to an increase in the study of international law, modern languages, and history at universities throughout Europe.

At the same time, permanent foreign ministries were established in almost all European states to coordinate embassies and their staffs. These ministries were still far from their modern form. Many had extraneous internal responsibilities. Britain had two departments with frequently overlapping powers until 1782. These early foreign ministries were also much smaller. France, which boasted the largest foreign affairs department, had only  70 full-time employees in the 1780s.

The elements of modern diplomacy slowly spread to Eastern Europe and arrived in Russia by the early eighteenth century. The entire system was greatly disrupted by the French Revolution and the subsequent years of warfare. The revolution would see commoners take over the diplomacy of the French state, and of those conquered by revolutionary armies. Ranks of precedence were abolished. Napoleon also refused to acknowledge diplomatic immunity, imprisoning several British diplomats accused of scheming against France. He had no patience for the often slow moving process of formal diplomacy.

After the fall of Napoleon, the Congress of Vienna of 1815 established an international system of diplomatic rank. Disputes on precedence among nations (and the appropriate diplomatic ranks used) persisted for over a century until after World War II, when the rank of ambassador became the norm.