About 8.58 million voters will be eligible to elect 32 legislators from among 456 candidates. Six districts will see balloting, including poverty-stricken Kaimur and Rohtas.
Most of the 8,849 polling booths on Friday are in rural areas.
The districts covered are Gaya, the birthplace of Buddhism, Aurangabad, Jehanabad, Arwal, Kaimur and Rohtas, which saw some horrific caste massacres in the 1980s and 1990s.
Some of these areas are also known as Maoist hubs, and officials admit security will be a major concern.
The stakes are high both for the Grand Alliance of the JD(U), RJD and Congress led by Chief Minister Nitish Kumar as well as the BJP-led NDA of Prime Minister Narender Modi, the two main contenders for power.
The second of the staggered five rounds will decide the political fate of former chief minister and HAM president Jitan Ram Manjhi, Speaker Uday Narayan Choudhary and BJP leader Prem Kumar, one of the contenders for the chief minister's post.
Manjhi, a BJP ally, is contesting from two seats: Makhdumpur in Jehanabad and Imamganj in Gaya. His son Santosh Kumar Manjhi is also in the fray from Kutumba and his son-in-law Devender Kumar Manjhi is contesting from Bodh Gaya as an independent.
The Grand Alliance is banking on OBCs and Muslims and sections of Dalits and EBCs to capture most of the 32 seats.
But the BJP is confident of the overwhelming support of upper castes along with sections of OBCs and EBCs along with Dalits, mainly Manjhi's castemen Mushahars as well as Paswans, who owe allegiance to LJP leader Ram Vilas Paswan, another BJP ally.
The BJP is keen to make its presence felt in the wake of the euphoria created by Modi's rallies in Jehanand, Aurangabad and Bhabhua.
This is also the strongest base of the Janata Dal-United (JD(U)) and the Rashtriya Janata Dal (RJD).
The region is home to a sizeable number of Yadavs, Lalu Prasad's community, and Muslims -- the two communities who helped the RJD to emerge as a major force in Bihar.
"The OBC-EBC-Dalit votes along with Muslims will be a decisive caste arithmetic," political analyst Soroor Ahmad said.
Officials say five helicopters, drones and 993 companies of paramilitary forces have been deployed for Friday, Additional Chief Electoral Officer R. Lakshaman said.
In the last two days, more than half a dozen bombs were seized in Gaya and Rohtas districts, planted allegedly by the Maoists to disrupt the elections, a police officer said.
The second round saw hectic and bitter campaigning by leaders from both sides including Modi, BJP president Amit Shah, Nitish Kumar, Lalu Prasad and Congress president Sonia Gandhi.
According to the Association for Democratic Reforms and the National Election Watch, 142 candidates in the second round face serious criminal charges including those of murder.
The staggered elections to pick a 243-member Bihar assembly will end on November 5. The result will be known three days later.
In the first phase on Monday, polling was held in 49 constituencies. The third round will be held on October 28.