The 61-year-old has worked his way back to the top during a coaching career which started with a season in charge of Racing, and also included a spell as Equatorial Guinea national coach.
His methods were really developed during six years in charge of Lugo, who he established in La Liga SmartBank (Second tier) for the first time in the small Galician club's history.
Summer 2017 saw Setien make the move to Real Betis, who he guided to sixth place in La Liga and Europa League qualification in his first season in charge.
And who could forget November 2018's thrilling 4-3 victory over Barcelona at the Camp Nou, the match which turned out to only home La Liga defeat of Valverde's two and half season reign as blaugrana coach. Barcelona fans who follow possession statistics closely will also know that Betis' 82.4% during a win over Leganes in October 2018 is the highest in La Liga over the last six years.
Last year also saw Betis win at the Santiago Bernabeu for the second consecutive season, making Setien the only rival coach to oversee wins away at both Real Madrid and Barcelona over the last 10 seasons.
Nevertheless, it was decided that Setien part company with Betis at the end of the campaign. "The team has gained an identity and this is almost above defeats or victories, it is tremendously important," he said as he departed.
Setien has now signed a contract with Barcelona until June 30, 2022, with his first game being Sunday's (January 19) La Liga clash against Granada at the Camp Nou. The tests then come quick and fast, with away trips to Valencia and Real Madrid in the coming weeks.
Mid-season managerial changes are never easy, but one thing is clear; the fact that Setien's approach fits so well with the footballing philosophy dominant at the Camp Nou over the decades will be a great help.