The most historically important and well-known is Rhodes, which, for millennia, has been the island from which the region is controlled. Of the others, Kos and Patmos are historically more important; the remaining nine are Astipalea, Kalimnos, Karpathos, Kasos, Leros, Nisyros, Symi, Tilos and Kastellorizo.
Other islands in the chain include Agathonisi, Alimia, Arkoi, Chalki, Farmakonisi, Gyali, Kinaros, Levitha, Lipsi, Marathos, Nimos, Pserimos, Saria, Stroggyli, Syrna and Telendos.
The Dodecanese have been inhabited since prehistoric times. In the Neopalatial period on Crete, the islands were heavily Minoanized (contact beginning in the second millennium BC). Following the downfall of the Minoans, the islands were ruled by the Mycenaean Greeks from circa 1400 BC, until the arrival of the Dorians circa 1100 BC. It is in the Dorian period that they began to prosper as an independent entity, developing a thriving economy and culture through the following centuries.
By the early Archaic Period Rhodes and Kos emerged as the major islands in the group, and in the 6th century BC the Dorians founded three major cities on Rhodes (Lindos, Kameiros and Ialyssos). Together with the island of Kos and the cities of Knidos and Halicarnassos on the mainland of Asia Minor, these made up the Dorian Hexapolis.
This development was interrupted around 499 BC by the Persian Wars, during which the islands were captured by the Persians for a brief period. Following the defeat of the Persians by the Athenians in 478 BC, the cities joined the Athenian-dominated Delian League. When the Peloponnesian War broke out in 431 BC, they remained largely neutral although they were still members of the League.
By the time the Peloponnesian War ended in 404 BC, the Dodecanese were mostly removed from the larger Aegean conflicts, and had begun a period of relative quiet and prosperity. In 408 BC, the three cities of Rhodes had united to form one state, which built a new capital on the northern end of the island, also named Rhodes; this united Rhodes was to dominate the region for the coming millennia. Other islands in the Dodecanese also developed into significant economic and cultural centers; most notably, Kos served as the site of the school of medicine founded by Hippocrates.
However, the Peloponnesian War had so weakened the entire Greek civilization's military strength that it lay open to invasion. In 357 BC, the islands were conquered by the king Mausolus of Caria, then in 340 BC by the Persians. But this second period of Persian rule proved to be nearly as short as the first, and the islands became part of the rapidly growing Macedonian Empire as Alexander the Great swept through and defeated the Persians in 332 BC, to the great relief of the islands' inhabitants.
Following the death of Alexander, the islands, and even Rhodes itself, were split up among the many generals who contended to succeed him.
The islands formed strong commercial ties with the Ptolemies in Egypt, and together they formed the Rhodo-Egyptian alliance which controlled trade throughout the Aegean in the 3rd century BC. Led by Rhodes, the islands developed into maritime, commercial and cultural centers: coins of Rhodes circulated almost everywhere in the Mediterranean, and the islands' schools of philosophy, literature and rhetoric were famous.
The Colossus of Rhodes, built in 304 BC, perhaps best symbolized their wealth and power.
In 164 BC, Rhodes signed a treaty with Rome, and the islands became aligned to greater or lesser extent with the Roman Empire while mostly maintaining their autonomy.
Rhodes quickly became a major schooling center for Roman noble families, and, as the islands (and particularly Rhodes) were important allies of Rome, they enjoyed numerous privileges and generally friendly relations. These were eventually lost in 42 BC, in the turmoil following the assassination of Julius Caesar in 44 BC, after which Cassius invaded and sacked the islands. Thereafter, they became part of the Roman Empire proper.
Titus made Rhodes capital of the Provincia Insularum, and eventually the islands were joined with Crete as part of the 18th Province of the Roman Empire.
In the 1st century, Saint Paul visited the islands twice, and Saint John visited numerous times; they succeeded in converting the islands to Christianity, placing them among the first dominantly Christian regions. Saint John eventually came to reside among them, being exiled to Patmos, where he wrote his famous Revelation.