The voting is expected to set in motion a full return to civilian governance after eight years of military rule under President Pervez Musharraf.
Musharraf seized power in 1999 by deposing the civilian government of Nawaz Sharif in coup.
The newly elected parliament will also have to confront major issues such as growing militancy and a sluggish economy.
Also to consider is whether to reinstate independent-minded judges who were removed by Musharraf during a state of emergency he declared in November last year.
If the opposition wins more than two-thirds of the seats in parliament, it is likely to try impeach Musharraf.
What is at stake?
Voters will get the chance to elect 272 members of Pakistan's National Assembly for a five-year term.
An additional 60 seats are reserved for women and 10 religious minorities.
These seats are distributed among parties based on how they fare in the election.
Musharraf, who was re-elected last year in October, will ask the winning party of the lower house to nominate a prime minister, once the new parliament convenes.
The nomination will then be subject to a majority vote in the legislature.
Voters on Monday will also pick legislatures in each of Pakistan’s four provinces.
In the last parliament the Pakistan Muslim League (PML), which backs the president, controlled 130 seats.
Pakistan holds elections for the lower house of parliament and assemblies in its four provinces on Monday.
More than 80 million Pakistanis aged 18 or over are eligible to vote.
More than 60,000 polling stations will open at 8 am (0300 GMT) and close at 5 pm (1200 GMT).
Early results are expected on Monday evening, but final official figures may not be available until Wednesday.
In recent decades, turnout has been modest, running about 40 per cent in the last national elections in 2002.
The National Alliance, which later became part of the PML, had 16 seats, and the party of Aftab Ahmed Khan Sherpao, interior minister in the PML-led coalition, held 19.
The Pakistan People’s Party (PPP) held 63 seats, and a six-party Islamist alliance called Muttahida Majli-e-Amal (MMA) held 59.
The Pakistan Muslim League of Nawaz Sharif, former Pakistan prime minister, also known as the PML-N or Nawaz League had 18 seats, while a pro-Musharraf regional party in Sindh province called Muttahida Qaumi Movement (MQM) held 18, and minor parties and independents accounted for the other 19 seats.
Several key figures are not running in this year's election.
Asif Ali Zardari, widower of the late Bhutto and co-chair of the PPP is a senator in the upper house of parliament and will not stand for the national assembly.
Sharif was disqualified from standing.