Two Democrats, both members of the state's congressional delegation, and three Republicans are vying for their parties' nominations.
Even before the bombings, the campaign had failed to capture the attention of voters compared with the 2010 special election following the death of longtime Sen. Edward Kennedy. Former Republican Sen. Scott Brown won the seat but was ousted last year in another high-profile race by Democratic challenger Elizabeth Warren.
A win would help Senate Democrats maintain a caucus edge of 55-45 as they press forward on major issues like immigration and gun control.
The Marathon bombs disrupted the political race, forcing the candidates to temporarily suspend their campaigns. The bombings also brought national security and terrorism issues to the fore in a race that was expected to turn on questions of the economy, gun control, taxes, immigration and abortion.
The Democratic primary pits U.S. Rep. Edward Markey, who has staked out more liberal positions, against fellow Rep. Stephen Lynch, a former ironworker who has tried to appeal to the party's working- and middle-class base.
Lynch, 58, has had to explain why he was the only member of the state's House delegation to vote against President Barack Obama's 2010 health care law, while Markey, who won his first elected office while in law school, has fended off efforts to portray him as a Washington insider.
Markey, 66, is better-funded, having raised $4.8 million through the end of the last reporting period, compared with $1.5 million for Lynch. He's also benefited from outside spending. Of the more than $2.2 million spent by outside groups, nearly 84 percent went to Markey, an Associated Press review of Federal Election Commission reports found.
The GOP primary race is pitting three candidates: former U.S. Attorney for Massachusetts Michael Sullivan, businessman Gabriel Gomez and state Rep. Daniel Winslow, former legal counsel for ex-governor and 2012 presidential nominee Mitt Romney.
Gomez, 47, has tried to portray himself as the new face of the Republican Party. The son of Colombian immigrants, Gomez learned English in kindergarten, then went on to become a Navy pilot and SEAL, earn an MBA at Harvard and launch a private equity career.
Sullivan, 58, has pointed to his national security resume, which includes helping investigate the Sept. 11 attacks and the failed attempt to blow up an airliner using shoe bombs.
The 54-year-old Winslow said he's the only candidate with experience in all three branches of the government.
After 12 years as a private attorney, Winslow was appointed to a judgeship on the state's district court in 1995. He served eight years and left to join Romney's administration as chief legal counsel.
The state's top elections official, Massachusetts Secretary of State William Galvin, has said fewer than one in five registered voters could end up casting ballots.
Polls are open from 7 a.m. to 8 p.m. The special Senate election is June 25.