The Large Hadron Collider has restarted, with protons making their way around its 27km tunnel for the first time since 2013.
Particle beams have travelled in both directions, inside parallel pipes, at a whisker beneath the speed of light.
Actual collisions will not begin for at least another month, but they will take place with nearly double the energy the LHC reached during its first run.
Scientists hope to glimpse a "new physics" beyond the Standard Model.
The beams have arrived a week or so later than originally scheduled, due to a now-resolved electrical fault.
The protons are injected at a relatively low energy to begin with. But over the coming months, engineers hope to gradually increase the beams' energy to 13 trillion electronvolts: double what it was during the LHC's first operating run.
So far, one beam of these tiny particles has been "threaded" through each section of the enormous circle, one by one, in preparation for the complete laps that will begin in the coming hours.
Physicists are frustrated by the existing Standard Model of particle physics. It describes 17 subatomic particles, including 12 building blocks of matter and 5 "force carriers" - the last of which, the Higgs boson, was finally detected by the LHC in 2012.
Prof Tara Shears, from the University of Liverpool, works on one of the LHC's four big experiments that will soon recommence their work, slamming protons together and quantifying the fallout.
"Of course in every particle physics experiment we've ever done, we've been wanting to make a big, unknown discovery," Prof Shears told BBC News.
"But now it's become particularly pressing, because with Run One and the discovery of the Higgs, we've discovered everything that our existing theory predicts."
In order to explain several baffling properties of the universe, things beyond the Standard Model have been proposed - but never directly detected.
These include dark energy, the all-pervading force suggested to account for the universe expanding faster and faster. And dark matter - the "web" that holds all visible matter in place, and would explain why galaxies spin much faster than they should, based on what we can see.
A theory called supersymmetry proposes additional particles, as yet unseen, that might fill in some of these gaps. But no experiment, including the LHC, has yet found evidence for anything "supersymmetrical".
Even the familiar and crucial force of gravity is nowhere in the Standard Model.
By taking matter to states we have never observed before - the LHC's collisions create temperatures not seen since moments after the Big Bang - physicists hope to find something unexpected that addresses some of these questions.
Debris from the tiny but history-making smash-ups might contain new particles, or tell-tale gaps betraying the presence of dark matter or even hidden dimensions.
But first we need collisions - due in May at the earliest - and then a steady torrent of data will make its way to physicists around the world, so that the massive analysis effort can begin.
Even when the results start to flow, we shouldn't hold our breath anticipating a breakthrough, according to Steven Goldfarb who works on the Atlas experiment.
Dr Goldfarb remembers working on Cern's previous atom smasher, the LEP collider, which commenced operations in 1989. Then, just like today, there was much excitement about staging higher-energy collisions than ever before.
"We thought at that time, perhaps we'd find the Higgs, perhaps we'd find supersymmetry. Many of the things we're looking for now, we looked for then," he told the BBC.
"In the end, we just measured the Standard Model more and more precisely. We put a lot of really good constraints on it, which taught us where to look for the Higgs - but there were no Eureka discoveries.
"And that could really be the case for the next several years."
Having the Higgs to aim for made the LHC's first chapter an unusual one, Dr Goldfarb explained.
"What was strange in the first run was we actually had a target that we were sure was in reach. We knew either we were going to find the Higgs boson, or some other mechanism that would replace it. There was no way you couldn't."
Now the work is exploratory, which is business as usual. And it is a slow business.
"We request patience! This is our job, usually," he said.
- BBC -