Italians are voting in four referendums, the most important of which is whether they want Italy to resume nuclear power production.
Anti-nuclear campaigners say the Fukushima disaster in Japan has helped sway public opinion against nuclear, the BBC reports.
The referendums are also seen as being a test of the popularity of Prime Minister Silvio Berlusconi.
Italy's last nuclear programme was abandoned in 1987 following the Chernobyl disaster.
The government says a nuclear industry is vital to supply about 20% of electricity needs by 2020.
But the BBC reports the disaster at the Fukushima plant, which was crippled by the tsunami and earthquake in northern Japan on 11 March, has changed the debate entirely.
People are also being asked to vote on water privatisation issues and whether government ministers can be exempted from court cases.
Mr Berlusconi is currently involved with four trials.
Results of the referendum are due on Monday