The festival this year is headlined by The Strokes, Florence and the Machine, The 1975 and Hozier.
Friday's lineup includes Billie Eilish at 7:30pm, Dermot Kennedy at 9pm and Hozier at 10:30pm on the main stage.
Saturday night will see other international stars grace the main stage.
Christine & The Queens will come on at 7:45pm, The 1975 at 9:15pm and The Strokes at 11:30pm.
Charlie XCX will perform at the Electric Stadium at 7pm.
Blindboy Boatclub of Rubberbandits fame will be speaking at the Podcasts stage at 12pm on Saturday also.
If comedy is more your style, Ardal O'Hanlon of Father Ted will be on the Comedy Stage at 6pm. Cork duo Lords of Strut, who wowed the crowds on Britain's Got Talent, will perform at 7:40pm. They are followed by Foil Arms and Hog.
The festival will close out on the Sunday with Kodaline at 8:30pm and Florence and the Machine at 10:30pm.
Both the HSE and the Gardaí have issued warnings about drug-taking ahead of Electric Picnic this weekend.
Speaking to The Irish Examiner, Detective Superintendent Brian Woods of the Drugs and Organised Crime Bureau, warned drug users that gardaí will be conducting "covert and overt policing" at the festival. He said substances will be seized and offenders could face prosecution.
This comes after shocking deaths and hospitalisations from suspected drug-taking at festivals across the country.
19-year-old student Jack Downey died at Cork University Hospital earlier this month after taking a substance suspected to be ecstasy at Indiependence festival in Mitchelstown.
The HSE also issued a drug safety statement ahead of the festival, urging people not to take drugs.
However, the HSE also said while they don't condone drug use, they need to be realistic.
The HSE issued these harm reduction tips: take small doses, do not mix drugs, stay cool and hydrated (but don't drink more than one pint of water per hour), tell your friends what you are taking, and to seek help if something goes wrong.
Eamon Keenan, the HSE’s National Clinical Lead for Addiction Services, also warned of high-strength MDMA/Ecstasy becoming more common across Europe, which presents a serious risk to life and health.