In the story, the Joestar lineage begins with George Joestar in the late 1800's, his son Jonathan is the first protagonist of the series and the first major antagonist of the series, Dio Brando is raised as his brother.
Though Jonathan dies before meeting any of his children, with his wife Erina, they have a child, also named George Joestar who marries Lisa Lisa (a child that Jonathan and Erina saved during the same incident that killed Jonathan) and they have a son Joseph (the second protagonist of the series).
He lives to see his children and it is his grandson Jotaro Kujo who takes the lead role in the third arc, while his illegitimate son Josuke Higashikata is the main character of the fourth.
With the fifth arc, the lineage between Dio and Jonathan is further muddied as the protagonist Giorno Giovanna is the son of both men, whereas the sixth arc returns to the main Joestar family with Jotaro's daughter, Jolyne Cujoh, the first female protagonist of the series.
In the alternate timeline that began in Steel Ball Run and continued in Jojolion, a lot of the same names are used for characters, though they turn out rather different.