The festival, which for a second year will last four days, is expected to draw an estimated 100,000 fans to Grant Park each day.
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Barricades are in place, streets are closed and Grant Park is ready to welcome those hundreds of thousands of people.
"That's going to give me so much anxiety but... I'm ready!" said Bri Hill, who is working Lollapalooza.
Chicago's own Chance the Rapper is one of the headliners. More than 170 other acts are booked on the event's eight stages.
Thursday night's headliners are Muse and Lorde, Friday it's Blink 182 and the Killers, Saturday features The xx and Chance the Rapper, and Sunday caps the festival with Arcade Fire and Justice.
Beyond the eclectic mix of performers, this year's Lollapalooza features larger video screens and sound systems, as well as a roller rink and arcade.
Attendees must wear their wristbands on their right wrist to get in at the main festival entrance and at the north entrance at Columbus Drive and Monroe Street. Security will be checking bags at all entrances for the usual prohibited items and for umbrellas, which are not allowed inside the festival this year even with the threat of rain.
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Large bags are not allowed, and al bags will be searched. Fans can re-enter the event three times per day, and there will be mobile medic teams in light blue shirts.
And because severe weather forced evacuations of Lollapalooza in 2012 and 2015, and almost last year, officials have designated three nearby parking garages as temporary shelters from any storms - Grant Park North and South garages, as well as the Millennium Park lakeside garage.
Emergency alerts will be sent out on the official Lollapalooza app, and video screens at the main entrance and all screens will broadcast any emergencies.
Although general admission packages quickly sold out, there is an official ticket exchange where people can buy and sell tickets at lollapalooza.com.
For additional information on allowed and prohibited items, as well as tips for attending Lollapalooza, click here.