Up to 120 cardinals will take the momentous decision over who will next lead the millions of Catholics around the globe.
The influential College of Cardinals must now meet in Rome and choose Pope Benedict XVI's replacement in a tradition dating back almost 1,000 years.
Since 1059, the selection of the next head of the Catholic church has been reserved to the College of Cardinals who are appointed by the pope.
Up to 120 cardinals, aged under 80 and from all over the world, will vote.
The college becomes immediately responsible for the day-to-day running of the church as Vatican offices are suspended but it is forbidden to take any decisions that would normally be reserved for the pope.
The cardinals' coming together is known as the conclave - from the Latin cum clave, meaning "with a key" in reference to them being locked in the Apostolic Palace until they produce a result.
Under regulations introduced in 1996, the cardinals will be housed in a building inside the Vatican's walls called the Domus Sanctae Marthae (St Martha's House).
They will move from there to the Papal Palace and the Sistine Chapel for the actual voting beneath Michelangelo's fresco of the Last Judgment.
Throughout the process they are sworn to secrecy and forbidden to speak to anyone not involved in the election.
Any breaches could result in their excommunication.
The cardinals wear a traditional black cassock with piping and red sash, a skull-cap, pectoral cross and ring throughout the process.
The 1996 voting rules now allow for just one method of selection, by two-thirds majority.
It replaced the traditions either of cardinals agreeing to one name without prior arrangement or by compromise.
The first vote is held on the afternoon of the first day if possible and there are then two ballots each morning and each afternoon thereafter until a result is declared.
Each cardinal enters a name on a special ballot paper and then, in order of precedence, puts it in a receptacle on an altar.
Three chosen cardinals, known as scrutineers, go through the votes one by one and announce the name on each paper.
The names are counted and if a name has received two-thirds of the votes, the pope has been elected.
If the first ballot does not produce a result, the process is repeated for three days, after which there is a day's rest for prayer, reflection and informal discussions.
The voting then begins again for a series of seven more ballots and then another break.
The process is repeated twice more and if there is still a stalemate, the chamberlain will declare a result can come from an absolute majority or by a vote on the two names that received the largest number of votes in the last ballot.
The candidate is then asked if he accepts and what name he wishes to take.
Tradition dictates that once a pope has been elected, white smoke will billow from the Vatican chimney - representing the burning of the ballot papers.
If the person elected is not already a bishop, he shall be immediately ordained and becomes the Bishop of Rome.
He is then announced to the people in St Peter's Square.
There is no coronation ceremony, but the pontificate is inaugurated at a ceremony in St Peter's, usually within a matter of days.