The NFC championship game after the 2011 season and again this year, and last season's 34-31 Super Bowl defeat to the Baltimore Ravens. And they have lost them all in a most frustrating fashion: Each time, with a great chance to win.
"I still think we're the best team," wide receiver Anquan Boldin said.
Quest for Six will have to wait at least one more year after the Niners lost a chance for a return trip to the Super Bowl in a 23-17 loss to archrival Seattle on Sunday.
For a franchise eager to rediscover the old dynasty, San Francisco will get a fresh start in 2014 at its new $1.2 billion Santa Clara stadium at team headquarters looking for another special season and to take the success one step further.
"It's great competition," Harbaugh said. "Not many people get to be in this arena. I'm proud of our guys for the fight they showed today and all season."
In a scene reminiscent of the way last season ended in the New Orleans Superdome in the Super Bowl, Colin Kaepernick threw a pass in the end zone intended for Michael Crabtree. This time, Richard Sherman deflected the ball right to Malcolm Smith for a game-sealing interception.
"The matchup was in my mind, one on one," Kaepernick said. "I feel like we should have won that game."
Yes, San Francisco (14-5) is left to head home for the offseason with a bitter taste again of what might have been, even with the daunting task for teams that reached the Super Bowl the year before to get back to the NFL's big stage.
Harbaugh knows special seasons can be fleeting. All he has to do is turn to big brother, John, whose Ravens failed to even reach the playoffs 11 months after winning a championship.
Kaepernick and the Niners knew one or two turnovers could cost them a return trip to the Super Bowl.
That had been the case in their past two visits to Seattle, so taking care of the ball became a top priority for San Francisco to beat the Seahawks on their home field.
Kaepernick went 14 for 24 for 153 yards with two sacks and two interceptions, and the 49ers committed three fourth-quarter turnovers - all by Kaepernick - that made the difference through the deafening noise of CenturyLink Field.
"I told him to keep his head up. He has no reason to drop his head, he played his butt off this entire season," Boldin said. "He made play after play."
These 49ers endured a daunting schedule and a pair of two-game losing streaks. They played without top 2012 wide receiver Crabtree for the first 11 games as he recovered from a torn right Achilles tendon and May surgery. San Francisco moved on in the postseason with tough road wins at Green Bay and Carolina.
"We played great as a team collectively," tight end Vernon Davis said. "If I look back on this season, I get excited because of where we came from and some of the things we were able to do as a team."
But there's something about Seattle lately for this group - three straight losses in which they have been outscored 94-33.
Even when the 49ers seemed to be the NFL's hottest team, riding an eight-game winning streak as they hit the road once more for one of the league's toughest venues.
"You can't point fingers," right tackle Anthony Davis said. "We came out here as a team, we win as a team, and we just lost as a team."
It hurt even more to see two key players from either side of the ball go down with serious injuries - All-Pro linebacker NaVorro Bowman with a likely torn left knee ligament, and left guard Mike Iupati with a left ankle that is believed to be broken.
"We had a shot," punter Andy Lee said. "That's what we wanted. It was a good year with these guys. Hopefully we can get back to work and come back all fine next year."