With both riders on 211 points, the result of Sunday's race will put daylight between the pair -- assuming both men don't crash out or retire -- in this tightest of seasons.
Lorenzo, who heads the standings only by virtue of his five race wins this term, says he feels at home at the historic motorsport venue.
"To be honest from the first time I was here, I just felt great," he told reporters ahead of the first practice session. "I always feel great here."
Rossi, meanwhile, knows he must fight tooth and nail to claim his 10th world title. The 36-year-old has seen his early lead in the championship overhauled, and, significantly, has never managed better than third place at Silverstone.
"Now it will be harder and harder -- a great fight," the Italian legend told Thursday's press conference. "I need to go faster and stay focused and work well."
Marc Marquez, meanwhile, is in relaxed mood despite trailing Lorenzo and Rossi by 52 points.
The champion knows his chances of retaining his title are virtually gone, but he has banished his disastrous early season form.
With two wins and two second places in the last four races, he retains a glimmer of hope.
"I need to do my 100% and be there every race and wait and see," the Repsol Honda rider told reporters.
"Here last year we had a really good weekend for me."
The weekend has some interesting subplots for local fans, with home favorite Cal Crutchlow announcing a new two-year contract with LCR Honda, and lead satellite rider Bradley Smith also putting pen to paper on a fresh deal with Monster Tech 3 Yamaha.
Both British riders attended a press event in London organized by MotoGP UK broadcaster BT Sport
this week, where Smith told CNN why he decided to stay put.
"I worked two-and-a-half years now to get to the point that I am, with a team that understands me, with a bike that I like to ride with a smiley face, with confidence, why would I want to go and chuck that all away when I know that I need to perform in the first six or seven races next season?"
Next season will see all teams sharing common electronics and Michelin replacing Bridgestone as MotoGP's tire supplier. Smith believes this alone meant a move was simply too risky.
"I'm shooting myself in the foot if I jump ship and I say OK I'm going to ride a new bike, work with a new team, with new tires, and new electronics," he told CNN.
"You know I'm making my life really, really difficult."
Less secure in his future is fellow Briton Scott Redding, whose debut year with the Marc VDS Honda team has been something of an ordeal.
The likeable 22-year-old is looking forward to next year's changes, and gave CNN a frank assessment of the current rules.
"The bulls**t this year with people on soft tires with a factory bike is ... it is unfair, you know?" Redding said.
"Because these guys I'm beating all the weekend, they put the soft tire in and they put me six positions back on the grid, so it is frustrating."
Meanwhile, home fans will be salivating at the prospect of the first British world champion since the late Barry Sheene in 1977.
Danny Kent leads the Moto3 World Championship and Silverstone will erupt if he can record his sixth race win of the season.
The 21-year-old is also weighing up his next move, with offers for both Moto2 and MotoGP rides on his table.
"When I'm riding the bike all I'm thinking about is riding the bike, but if there's too much on your mind you start making mistakes, so I'd like to get the future sorted as soon as possible," he told CNN.
Sunday's races, in what should be typically capricious weather conditions, should leave the future clearer for many of this MotoGP season's stories.