The 63-year-old three-time champion trainer has won the sport's biggest prizes - he is the most successful handler at the Cheltenham Festival with 51 winners - but the National has eluded him since his first runner in 1979.
Henderson will saddle four of the 40-strong National field and said he has his "best chance yet".
"It doesn't bug me but I'd love to win it," he said after a successful day yesterday. "You need the right ammunition. I'll keep trying."
Henderson's quartet are headed by the classy Long Run, the Cheltenham Gold Cup winner in 2011 and twice successful in the King George VI Chase, who will be ridden by amateur Sam Waley-Cohen.
The trainer also has Hunt Ball, Shakalakaboomboom and Triolo D'Alene.
"Every now and then the right horses come along. We've had some close shaves, we've been second twice. It's there but it's avoided us so far," Henderson said.
His near misses came with his first runner Zongalero in 1979 and The Tsarevich, who was also second eight years later. But since 1991 only two of his entries have finished the marathon jumping test.
If Henderson misses out again today, he could have a future National star in Ma Filleule who won the Topham Chase in impressive style yesterday in a race contested over the testing National fences.
Henderson and Irishman Barry Geraghty also enjoyed success with Josses Hill and Beat That on Friday but four jockeys suffered injury in the Topham Chase which has put their National participation into question.
Paul Carberry (precautionary x-rays for possible pelvic injury) and Mickey Fogarty (further assessment on a back injury) were taken to hospital while Andrew Tinkler has taken a bang on his wrist and Noel Fehily has an elbow problem.
Carberry is due to ride leading National hope Monbeg Dude who is part-owned by former England rugby captain Mike Tindall and fellow players James Simpson-Daniel and Nicky Robinson.
Monbeg Dude, whose jumping has been brushed up by Queen Elizabeth's granddaughter Zara Phillips, the 2012 Olympic equestrian silver medallist who is married to Tindall, is likely to start second favourite behind the Rebecca Curtis-trained Teaforthree.
Teaforthree gave connections a huge thrill when third 12 months ago and ran a respectable race in the Gold Cup. His trainer Rebecca Curtis thinks he heads to Aintree in even better shape than last year.
"He took to the Grand National fences last year," said the Newport handler. "I thought he ran a blinder in the Gold Cup, it was the ideal prep run. We didn't want to go seven weeks after his run at Ascot and I think it put him spot-on.I'd have to say I think he's in better form than last year.
Paul Townend, so often in the shadow of Ruby Walsh, gets his big chance to make headlines of his own with the potentially plum ride on Prince De Beauchene. Dual National winner Walsh broke an arm at the Cheltenham Festival, leaving stable No.2 Townend to take the ride on a horse that has missed the last two runnings through injuries of his own when he would have been a leading contender.
"Touch wood he jumps well at home. He's never run over the National fences before and has missed the last two when it's been his aim," said former Irish champion Townend, who bagged a Grade One prize at the meeting on Boston Bob yesterday, in the same colours of Graham Wylie.
"The trip is a bit of an unknown, but I think he will stay. He ran a nice race in the English Hennessy but faded out of it with a big weight, and was running well in the Lexus until he made a mistake. He brings a touch of class, has a lovely racing weight and if he gets into a rhythm you never know."