The 31-year-old from Victoria is Garmin's chosen candidate for the prestigious general classification competition. Simply put, his fellow Garmin riders will be working to put him atop the podium when the race ends May 27.
Hesjedal believes the gruelling Giro is well suited to his talents — and durability.
"The third week is definitely where there's the most to gain and lose, especially in the overall classifications," he told The Canadian Press from Denmark, where the race starts with an individual time trial.
"This race is definitely packed well in the last week, especially after the first half. I'm hoping my characteristics will come through and I'll be at my strongest in the last week."
The 3,503.9-kilometre race ends with a team time trial in Milan.
Hesjedal is part of a global field that features 198 riders from 22 different countries, according to organizers.
There is other Canadian content in the storied race.
The new Australian Greenedge team features Christian Meier of Sussex, N.B., and Svein Tuft of White Rock, B.C.
And Dominique Rollin of Boucherville, Que., is part of the French FDJ-Big Mat team.
Toronto's Michael Barry is recovering from elbow surgery and expects to return to action for Team Sky at the Tour of Norway in mid-May.
The Giro is the first of the three elite Grand Tour stage cycling races on the calendar followed by the Tour de France and Vuelta a Espana.
This is the third Giro for Hesjedal, who has risen up the ranks in recent years due to his gritty performances in the Tour de France.
"In a lot of ways it can be harder than the Tour," said Hesjedal. "It's earlier in the year. The weather can be worse.
"The history's just as rich. All the great champions have won the Tour and the Giro, and use the Giro as an important part of their season. I think Italians would say the Giro's bigger and better than the Tour, but for me it's a hard race ... It's just as hard (as the Tour), that's for sure."
His breakthrough year was 2010 when he finished seventh at the Tour de France, taking over Garmin's lead role after injuries derailed some of his teammate's chances.
Last year, his Tour charge was slowed by a painful crash on Stage 7.
Hesjedal paced the peleton for long stretches as he secured position for other members of the then Garmin-Cervelo team, which finished first in the team standings. The Canadian finished 18th overall.
Hesjedal, a former mountain biker, made his Giro debut in 2005. It marked his first Grand Tour in his first year of only racing on the road.
"It was all big and new and I had done a very hard spring leading up to that," he recalled. "Unfortunately I crashed pretty badly on the fifth stage — still pretty early. So I had a pretty tough go at it. All I remember is suffering every day and I only made it until the end of the second week."
Italy's Paolo Savoldelli, a teammate on his Discovery Channel team, went on to win the race.
In 2008, it was the first race for his current team with American Christian Vande Velde emerging with the pink jersey after they won the opening individual time trial.
"It was a very hard Giro to finish," Hesjedal said of 2008. "I got through it and that set me up to do my first Tour de France later that summer. So the Giro's been pretty instrumental in points of my career."
Hesjedal's Garmin team has its sights set on other prizes at this year's race. American Tyler Farrar, for example, will be challenging for the sprint title.
The Canadian prepared for the Giro at the Tour de Romandie, pulling out on the second-to-last stage to get an extra recovery day in advance of this race.
Hesjedal is not thinking of the Tour de France, saying the Giro "is the big objective right now."
"If the Giro goes good, that is just perfect for the Tour," he said. "With Christian Vande Velde definitely focusing on the Tour, so if anything I'll be going to the Tour to support him like he's going to support me here.
"And you never know how the race unfolds. I mean I never went to the 2010 Tour looking to ride the classification either. You just don't know, but I'll be there. If it's not supporting someone else, I'll have my opportunities to go hunting for some stages and that sort of thing.
"Whatever the goals of the team are, that's all we focus on."
It's a big summer for the Canadian, who hopes to go straight from the Tour de France to the Olympic road race in London. The Canadian Cycling Association will announce its team later this summer, with Hesjedal the leading candidate to fill Canada's one spot in the road race.
"I want to go, I want to represent Canada. I know I can be in a good place after the Tour of the season goes as it's supposed to."
Hesjedal raced in both the road race and time trial at the 2008 Beijing Games.