The rivalry has dominated much of the current generation, and while Kobe Bryant will not suit up, the Lakers will undoubtedly find other stars to carry the load.
At the same time, the Spurs will look towards their triumvirate of stars for leadership, as they look to get on track after a three-game skid to end the regular season.
Each team had displayed a great level of talent throughout the season, but only one will make it out of the first round on top.
The question is, who will that be?
Info: Sunday April 21, L.A. Lakers at San Antonio, 3:30 p.m. (ET)
Though the Spurs finished the regular season with the better head-to-head record, the Lakers made sure that they enjoyed the last laugh.
The Kobe-less squad, playing its first game since the injury to its star, quickly showed the world that it could compete without its leading man.
The Spurs struggled throughout and ultimately fell five points short of the series sweep.
Having lost their last three games, the Spurs will enter the playoffs struggling, but San Antonio—being the epitome of professionalism—has the potential to bounce back.
Coach Gregg Popovich will demand a dose of nasty, and with Tony Parker, Tim Duncan and the rest of the squad hungry for revenge—they won't disappoint in front of their home crowd.
Prediction: Lakers 91, Spurs 100
Info: Wednesday April 24, L.A. Lakers at San Antonio, 9:30 p.m. (ET)
After dropping Game 1, the Lakers will be the ones seeking revenge. With Steve Nash having adjusted back into the lineup, L.A. will find itself up early and in total control throughout the first half.
However, the Spurs have fought back from incredible postseason deficits before and the veteran team will pull it together in the second half.
Increased playing time for Steve Nash will lead to offensive dominance from Tony Parker and crunch-time star Manu Ginobili will announce his return with a big fourth quarter in which the Spurs will cut down the Lakers' lead.
With the momentum going their way (in addition to a few Hack-a-Dwights), the Spurs will complete the comeback, closing out the Lakers in the final moments—though the final margin will remain small.
Prediction: Lakers 104, Spurs 107
Info: Friday April 26, San Antonio at L.A. Lakers, 10:30 p.m. (ET)
Though the Spurs will enter Game 3 with momentum, a change of scenery will prove beneficial for the Lakers.
With the Staples Center decked out in purple and yellow, the team will set out to impress the home crowd and fight for a much-needed home victory.
With the spotlight shining directly on Dwight Howard, the Lakers' big man will deliver throughout the contest, proving his status as L.A.'s next star.
With just one day's rest, San Antonio's veterans will enter the game tired from the exhausting endeavors of Game 2.
Howard and Pau Gasol will dominate the Spurs' post players from start to finish, picking up a huge win at home and cutting the series gap between the two teams.
Prediction: Spurs 89, Lakers 101
Info: Sunday April 28, San Antonio at L.A. Lakers, 7 p.m. (ET)
It's been said that the playoffs don't begin until a team wins on the road, making Game 4 incredibly important to the Spurs' first-round success.
Fresh off a win, the Lakers will look to tie the series at two apiece, but after being embarrassed in the previous matchup, Gregg Popovich will ensure that the Lakers' efforts fall short.
With Tony Parker leading the attack, the Spurs will take an early lead, but a second-half comeback will ensure that the victor remains undecided until the closing moments.
Despite the late push, the Spurs will squeak out the close win, hitting a game-winner in the closing seconds.
Whether it be Ginobili, Parker or even Danny Green (again), the Spurs will edge out their West Coast opponents, winning what will ultimately prove to be the most important game of the series.
Prediction: Spurs 112, Lakers 111
Info: Tuesday April 30, L.A. Lakers at San Antonio, TBD
Having rediscovered their mojo, the San Antonio Spurs will travel back home with momentum behind them.
With a first-round victory just inches away, the team will play more motivated than ever, using the support of the crowd as that extra push that puts it over the top.
With the veterans having suffered significant injury in the previous matchup, Game 5 will fall to Kawhi Leonard to take control.
Younger and more talented than Metta World Peace, Leonard will make a statement, enjoying a career-best game.
From start to finish, the game will be a San Antonio spectacle, as the Spurs pick up their final win and extend their postseason run by another round.
Prediction: Lakers 101, Spurs 118