Having played 12 times since the turn of the century alone, the two sides are no strangers to one another, with the Blues unbeaten in their last seven outings against the Spanish side.
Here are 5 classic clashes between the two European giants:
5. Chelsea 4-2 Barcelona, 5-4 agg (Last 16, 2004-05)
A game most remembered for a stupendous goal from then-World Player of the Year Ronaldinho, saw Jose Mourinho's Chelsea overcome a 2-1 deficit from the Nou Camp to reach the quarter finals of the tournament.
The hosts coasted to a 3-0 lead inside 20 minutes, with Eidur Gudjohnsen opening the scoring before Frank Lampard and Damien Duff netting within two minutes of each other to send the west Londoners into dreamland.
A quick-fire brace from Ronaldinho put the visitors ahead on away goals. The Brazilian's second strike was particularly stunning, taking the ball down on the edge of the box, surrounded by Chelsea blue, only to nonchalantly stroke it past Petr Cech into the bottom corner.
Captain John Terry popped up from a corner 15 minutes from time to head home, and seal a quarter final tie with Bayern Munich.
4. Chelsea 1-2 Barcelona (Last 16, 2005-06)
With Frank Rijkaard's side still smarting from being knocked out the year before, they returned to west London looking for revenge on the Blues, themselves well on their way to a second straight Premier League title.
Chelsea found themselves down to ten men late in the first half when Asier del Horno was sent off for a foul on Lionel Messi, with the 18-year-old running the Spaniard ragged up to that point. Jose Mourinho memorably quipped after the game that the Argentine must have learned play-acting living in a city of culture like Barcelona.
Despite being a man down, Mourinho's men took the lead, with a Frank Lampard free-kick causing Thiago Motta to score an unlucky own goal just before the hour mark. With 20 minutes left to play, it was the home side's turn to net at the wrong end, with John Terry unknowingly nodding past Petr Cech to level the score.
Just ten minutes later, Samuel Eto'o rose highest from a Rafael Marquez cross to power home and secure a crucial second goal for the Blaugrana. It was enough to kill off the match and take a lead back to the Nou Camp, where they saw out a 1-1 draw for the aggregate victory, on their way to the trophy in May.
3. Barcelona 2-2 Chelsea (Group Stage, 2006-07)
The two sides were matched up again only months later, with the English and Spanish champions drawn together in Group A for the 2006-07 season. Having narrowly won the home tie 1-0, Chelsea travelled to Spain looking to secure qualification for the knockout rounds.
They got off to a bad start, with Deco putting the holders in front after just three minutes, curling past compatriot Hilario. Frank Lampard levelled after the break with an outrageous effort, chipping Victor Valdes from a seemingly impossible angle on the left wing.
Ex-Chelsea man Eidur Gudjohnsen restored the hosts' advantage just before the hour mark, turning home a Ronaldinho cross. The visitors pushed for an equaliser, and got their reward when Didier Drogba pulled them level with a stoppage-time finish, coolly slotting into the net from a John Terry header to earn a last-gasp point.
2. Chelsea 1-1 Barcelona, 1-1 agg (Semi Finals, 2008-09)
Mention the name Tom Henning Ovrebo in certain parts of west London, and you are certain to be greeted with glares and all manner of profanity. Infamous amongst Chelsea fans for terrible refereeing, the away goals semi-final defeat to Pep Guardiola's Barcelona is one that will live long in the memory.
Looking to set up a second straight all-English final against Manchester United after their Moscow heartbreak, the Blues earned a goalless draw in Spain, and took the lead in the return leg through a brilliant Michael Essien volley after only nine minutes.
Guus Hiddink's men had four notable penalty appeals, all turned down by official Ovrebo, to the bemusement of the Chelsea players, in their search for a decisive second goal. The hosts thought they had done enough to seal a place in Rome, only for Andres Iniesta to pop up on the edge of the box three minutes into injury time to fire a stunning effort home and break Chelsea hearts.
With emotions running high after the perceived injustive, Didier Drogba launched into a televised, expletive-filled outburst at the referee after the game, earning himself a three-match European ban, and the club an £85,000 fine for misconduct.
1. Barcelona 2-2 Chelsea, 2-3 agg (Semi Finals, 2011-12)
The most recent and famous meeting between the two sides, it saw caretaker manager Roberto di Matteo mastermind a sensational aggregate victory to take Chelsea into the 2012 final against Bayern Munich, against all odds.
Holding a 1-0 lead from the first leg, the Blues were pegged back midway through the first half when Sergio Busquets put the hosts in front. John Terry was shown a straight red for a petulant knee to Alexis Sanchez.
Andres Iniesta curled past Petr Cech five minutes later to give Barcelona the lead, and seemingly the tie. Ramires replied almost instantly with a goal from nothing, chipping Victor Valdes from the edge of the box to give the ten men hope.
Just after half-time, Didier Drogba gave a penalty away to future Chelsea man Cesc Fabregas, only for Lionel Messi's accurate penalty to hit the bar. The Argentinian has still never scored against Chelsea. The visitors had ten men behind the ball for the entire second period and stood firm, with much-criticised Fernando Torres' late goal ensuring their place in the Munich showpiece.