But he then turned to hand cycling, soaring to the top of that sport with gold medals at the 2012 paralympic games in London.
Now, at the age of 47, Zanardi - who last raced in F1 in 1999 with Williams - is returning to four wheels once again.
He has been signed to drive a modified BMW in the Blancpain Sprint Series.
"Even after leaving the sport in 2009, I was still a racing driver at heart," said Zanardi.
BMW motor sport chief Jens Marquardt said: "From both a human and a sporting aspect, Alex is a role model to all of us."