A year ago the double world champion and victor of London and New York City titles followed up her Boston win by taking silver at the World Championships in London.
Security at the marathon was heightened after the bombings, police say they are ready for Monday's race.
Can Kenya's 38-year-old Edna Kiplagat, pictured en route to world marathon silver last year, retain her Boston Marathon title against strong America opposition?
Aside from Flanagan, other American women are expected to be strong contenders this year, including Jordan Hasay, Molly Huddle, Deena Kastor and Desiree Linden.
Huddle has been a success at shorter distances, although her only marathon result was a third-place finish at NY in 2016.Flanagan, 36, missed last year's race with an injury but won at NY with extra rest.
On the men's side, American Galen Rupp - who won the Chicago Marathon in October - looks to emerge victorious after a second-place finish in the 2017 Boston Marathon.
"Her doctor and team have made the decision that Jordan needs to take time to recover fully so there is no long-term injury", the statement said, adding that officials support Hasay's decision and invite her to return to Boston in 2019.
General view of the pack of elite women near the start of the 2017 Boston Marathon.
Meanwhile, Kirui aims to repeat last year's success.
The two-time world champion has also won at London in 2014 and NY in 2010.Kirui is trying to become the first back-to-back men's victor at Boston since compatriot Robert Kipkoech Cheruiyot in 2006-2008.
The fastest man in the field, however, is Ethiopia's Tamirat Tola, second behind Kirui at last summer's World Championships, who set a personal best of 2:04:06 in January at the Dubai Marathon.