The Liverpool-born Briton also produced and co-directed the acclaimed documentary "Restrepo," which won an Oscar nomination.
"He really wanted to get the pictures but at the same time I had the impression he was a very responsible person," Tiziana Prezzo, an Italian journalist who was in Misrata two days earlier, told AFP.
"He was one of the last people I met in Misrata. Now that he's not alive anymore... it's shocking," she said.
Chris Hondros, also 41, an American with the Getty photo agency, was seriously wounded in the same incident.
The two journalists wounded were Guy Martin, a freelance photographer working for the picture agency Panos, confirmed the British Foreign Ministry and Panos, and American Michael Brown who was working for Corbis, confirmed the agency's director of communications Dan Perlet.
The four journalists were hit by mortar fire on Tripoli Street, the main thoroughfare and focus of fighting in Misrata, which has been under siege for almost two months by Libyan leader Moamer Kadhafi's forces.
Hetherington's family said in a statement released to Vanity Fair that it was "with great sadness we learned that our son and brother" Hetherington was killed, saying "he will be forever missed."
On Tuesday, he sent his last post to his Twitter account, where he said: "In besieged Libyan city of Misrata. Indiscriminate shelling by Qaddafi forces. No sign of NATO."
Journalists increasingly have come under fire in the ongoing conflict in Libya.
In the courtroom of Benghazi, seat of the opposition, photographs of missing journalists plaster the walls alongside a portrait of Ali Hassan al-Jaber, an Al-Jazeera cameraman killed on March 12 in an ambush near Benghazi.
Jaber was the first foreign journalist killed in Libya since the beginning of the uprising against Kadhafi on February 15. Numerous journalists have been detained and often mistreated by the Libyan regime.
A spokesman for the rebel Transitional National Council (TNC) said that eight foreign journalists and six Libyan colleagues are currently being held by Kadhafi's forces.
TNC spokesman Abdel Hafiz Ghoqa said journalists were free to work unhindered in rebel-held areas of eastern Libya.
"Even under the difficult conditions imposed to us by the regime, everyone is free to say what they think and move where they wish, journalists and citizens alike," he said.
A growing number of media companies are hiring security consultants for advice on their movements around the fluctuating front line between Kadhafi's loyalists and rebel forces.