Michael Essien and Kevin-Prince Boateng are both returning after extended breaks from international football to play for Ghana at the World Cup, and Andre Ayew is also likely to be one of the country's pivotal players in Brazil.
Ghana narrowly missed becoming the first African team to reach the semifinals at a World Cup when it lost to Uruguay in the quarterfinals in 2010. The Black Stars had a penalty in extra time, but missed from the spot. Uruguay won in a shootout.
The core of that to team is back for another try.
Here are five players to watch:
Often outstanding for European clubs Chelsea, Real Madrid and now AC Milan, the hard-working central midfielder has missed many of Ghana's big moments recently, including the last World Cup, because of injuries and then his sabbatical.
The 31-year-old Essien returned to the squad last year and his ability to power Ghana's World Cup challenge from the middle of the field may be crucial to the Black Stars' hopes of reaching the latter stages.
Boateng made himself unavailable for selection in 2011 and only returned late last year for the end of the qualifying campaign for Brazil, when he was eased back into the team by Ghana coach Kwesi Appiah.
He scored in the last playoff match against Egypt and offers big-game experience from Europe's top leagues.
A German youth international from under-15 level, Boateng chose Ghana, his father's country, at senior level. His brother Jerome plays for Germany, which Ghana will face in the group stage at the World Cup.
Gyan missed a crucial penalty in extra time against Uruguay that could have put the Black Stars into the 2010 World Cup semifinals. He also missed from the spot in the semifinals of the African Cup in 2012 as Ghana was eliminated.
The 28-year-old forward has taken on the captaincy and often fights a lone battle as Ghana's solitary striker.
Asamoah plays on the left side of defense or midfield and can also operate as a central midfielder with the ability to push forward and create and score goals.
At 25, the Juventus player already has six years of experience with Ghana and six years in Serie A.
The 24-year-old winger has pace and skill and can also play as a second striker, but has sometimes been a troublesome figure in the Ghana setup.
Ayew was excluded from the squad for the last African Cup after failing to report for duty at a pre-tournament training camp. He has since made up with coach Kewsi Appiah and is one of Ghana's most creative players.