Shahzad introduced the world to hitherto unknown Al-Qaeda figures including Sheikh Essa. He had interviewed several leading militants long before they became internationally known, including Sirajuddin Haqqani and Qari Ziaur Rahman.

Shahzad interviewed Ilyas Kashmiri shortly after Ilyas was appointed chief of Al-Qaeda’s military committee.His  last book Inside Al-Qaeda and the Taliban: Beyond Bin Laden and 9/11, was published shortly before his death.

Shahzad's work was regularly reproduced in Pakistani English dailies including the Daily Times, the Nation and The Post, and in Urdu newspapers such as Mashriq Peshawar and Aaj Peshawar. His articles were reproduced in many English dailies in Afghanistan and Bangladesh, as well as in local-language dailies. His work was often quoted in the US, Canadian and Indian press.

Saleem was an associate of the Pakistan Security Research Unit of the department of Peace Studies of the University of Bradford. In November 2006 he was held in Taliban captivity in the Helmand Province of Afghanistan for a few days. He wrote a detailed account of his days in captivity and time he spent with the Taliban in a series, "In the Land of the Taliban" published in Asia Times Online.

Shahzad disappeared on the evening of 29 May 2011 in Islamabad. He reportedly left his home around 5:30 pm local time that evening to take part in a TV show scheduled for 6:00 pm, but at 5:42 pm his cell phone was switched off and he failed to arrive at the television bureau. A complaint was lodged with the police the following morning. On May 31 it was reported that his car had been found with an unidentified body.

Later on the same day, his family confirmed that he was dead, with police stating that his body had been found in a canal in Mandi Bahauddin district and his car found at Sarai Alamgir in Pakistan's northern Gujarat district, some 150km (93 miles) south-east of the capital. His car was found about 10km (six miles) away.

In autumn 2010, less than a year before his death, Shahzad wrote to Human Rights Watch predicting that he might be detained by Pakistan's Inter-Services Intelligence (ISI) intelligence agency. According to a researcher at Human Rights Watch, Ali Dayan Hasan, "the manner in which this killing took place echoes other documented cases in which Pakistan’s intelligence services, chiefly the ISI, have been involved." Hasan is calling for a full investigation into his killing.

Leading Pakistani journalists reacted strongly to the murder. Badar Alam, editor of the Herald magazine, said in connection with the killing, "This only means this country is dangerous for anyone trying to work as a journalist. ... Regardless of your professional standing, you are under threat. This is not the first time that agencies have been involved in intimidating journalists."Pakistani Prime Minister Yousaf Raza Gillani ordered an immediate inquiry into the kidnapping and murder.