Ptolemy had been expanding his power into the Aegean Sea and to Cyprus. Antigonus thus resumed the war with Ptolemy in 308 BCE, beginning the Fourth War of the Diadochi. Antigonus sent his son Demetrius to regain control of Greece, and in 307 BCE he took Athens. Demetrius then turned his attention to Ptolemy, invading Cyprus and defeating Ptolemy's fleet at the Battle of Salamis-in-Cyprus.

In 306, Antigonus attempted to invade Egypt, but storms prevented Demetrius's fleet from supplying him, and he was forced to return home. With Cassander and Ptolemy both weakened, and Seleucus still occupied by attempting to assert his control over the East, Antigonus and Demetrius now turned their attention to Rhodes, which was besieged by Demetrius's forces in 305 BCE. The island was reinforced by troops from Ptolemy, Lysimachus, and Cassander. Ultimately, the Rhodians reached a compromise with Demetrius – they would support Antigonus and Demetrius against all enemies, save their ally Ptolemy. Ptolemy took the title of Soter ("Savior") for his role in preventing the fall of Rhodes, but the victory was ultimately Demetrius's, as it left him with a free hand to attack Cassander in Greece. Demetrius thus returned to Greece and set about liberating the cities of Greece, expelling Cassander's garrisons, and the pro-Antipatrid oligarchies.

Cassander held counsel with Lysimachus, and they agreed on a joint strategy that included sending envoys to Ptolemy and Seleucus, asking them to join in combatting the Antigonid threat. With assistance from Cassander, Lysimachus overran much of western Anatolia, but was soon (301 BCE) isolated by Antigonus and Demetrius near Ipsus.