The 2001 telethon brought in a record $56.8 million and Lewis, ever optimistic, hopes to surpass that total this Labor Day in a 21.5 hour telecast from CBS Television City in Hollywood.
The MDA telecast, first of its kind, has become a television juggernaut of vaudeville-like acts to battle more than 40 neuromuscular diseases. The funds provide services for children and adults through professional and public health facilities education and training nationwide.
Some 76 cents of each dollar MDA spends goes directly to program services. Lewis is paid nothing. All entertainers and performers donate their time for the cause.
Running from 9 p.m. (EDT) Sunday, Sept. 1 through 6:30 p.m. Mon., Sept. 2, pledges will be phoned into local TV stations and to national telephone numbers throughout the country.
The big show will be broadcast on the "Love Network" with local stations airing hourly segments featuring information regarding MDA's programs in their communities.
Among musical stars participating this year are Glen Campbell, Tammy Cochran, Jim Stafford, Aretha Franklin, Patti LaBelle, Little Richard and Nancy Sinatra. Others include Jack Jones, Clint Holmes, Maureen McGovern, Steve Lawrence, Shirley Caesar and Take 6.
Also providing music and comedy will be Carrot Top, Sarah Chang, Chicago, Billy Crystal, Fyvush Finkel and Norm Crosby. As in previous years, there will be more performers on the telethon than can be found anywhere else in a single TV show.
In addition to entertainers, the telethon will feature interviews with leading physicians and scientists discussing MDA's progress.
But the biggest star will be Jerry Lewis who, with partner Dean Martin, conceived the first MDA telethon back in 1966 when it was broadcast only in New York City.
It has grown to become the single most important fund-raising event for MDA and provides 88 free camping sessions for thousands of youngsters with neuromuscular disease and support groups of family members. Its funds assist with purchase and repair of wheelchairs, leg braces and professional and public education.
As medical science progresses, MDA funds have grown to aid gene therapy, stem cell therapy to correct Duchenne muscular dystrophy.
It has branched out to help find treatment for Lou Gehrig's disease, myotonic muscular dystrophy (ALS) and related diseases in adults.
An MDA spokesman said a million Americans are affected by neuromuscular diseases and some 250,000 are victims of muscular dystrophy.
More than 4,000 MDA kids attend MDA summer camps each year at a cost of $525 per camper, with no charge to families.
More than 75,000 visits are made each year to MDA's 230 hospital-affiliated clinics and 28 MDA/ALS centers.
MDA grants awards to 400 teams of scientists and physicians worldwide.
The annual MDA telethon has become a giant of strength and hope for overcoming the devastation of neuromuscular diseases, enabling medical science to make astonishing progress in its battles.
As MDA's year-around national chairman, Lewis has been the organizations top volunteer for 50 years.
He gives more time to the development and promotion of the telethon than to his own performing career.
The 76-year-old comedian is passionate about his devotion to the MDA cause, determined to raise funds year around, establishing beachheads for scientific and medical forays against the crippling, killer diseases.
His longtime friend and side-kick Ed McMahon will be the tireless anchor of the telethon, as he has been for 35 years.
Hosting segments of the show from Las Vegas will be Charo with singer Andy Williams playing emcee from Branson, Mo.
An MDA spokesman said nearly a million volunteers across the country will be involved in the telethon during Labor Day weekend.
An astonishing 80 percent to 103 percent (due to contributions of more than was pledged) of pledges actually are fulfilled each year
Of his overwhelming efforts on behalf of MDA, Lewis said this week, "Every year I approach the telethon with the same goals.
"I want to entertain the audience, and to educate the public about these diseases and the kids and adults they affect. And if I do my job, we'll be able to raise at least one dollar more than we did last year."
In response to questions asking WHY Lewis works all year long to promote the telethon and to bring in pledges, he responds, "It's not important WHY I do it -- it's just important that I DO it."
Always an emotional man, comedian Lewis truly believes in giving back something to his fellow citizens.
Notable deaths of 2014 [PHOTOS]