The format of the show, and Matthews' interview style, can lead to confrontations. Perhaps the most famous examples came during the 2004 presidential campaign. On August 19, conservative commentator Michelle Malkin appeared on the show and raised the question of whether Democratic candidate John Kerry's Vietnam War wounds could have been "self-inflicted", saying that such questions were "legitimate". Matthews repeatedly asked Malkin if she thought that Kerry "shot himself on purpose" in order to avoid combat or to gain accolades, noting that such an act would constitute a criminal offense. Matthews challenged Malkin to "say to me right now that you believe he shot himself to get credit for a Purple Heart-- on purpose." Malkin refused to answer, instead referring to allegations made by some of Kerry's former fellow soldiers. Matthews told Malkin that Hardball "is not a show for this kind of talk." Malkin asked if Matthews didn't wonder whether Kerry's wounds may have been self-inflicted, to which the host responded, "No! I don't, it's never occurred to me.
Days later, then-U.S. Senator Zell Miller, (D-Georgia), a Democrat who supported Republican President George W. Bush, appeared on Hardball. Miller had just given the keynote address at the Republican convention. Matthews took Miller to task for his statement that soldiers, not reporters, are responsible for freedom of the press, accusing the Senator of making the comment only "to get an applause line against the media at a conservative convention." Miller had also criticized Kerry's record on national defense issues during his speech, prompting Matthews to ask if the Senator believed that Kerry did not want to "defend the country." During a heated exchange in which each man interrupted the other several times, Miller shouted at Matthews to "get out of my face" and angrily stated that he wished "we lived in the day where you could challenge a person to a duel." He also made reference to the Malkin interview, telling Matthews not to "pull that stuff on me like you did that young lady, when you had her there browbeating her to death. I'm not her.
On June 26, 2007, Ann Coulter was the guest when Elizabeth Edwards, wife of Democratic Presidential candidate John Edwards, made a surprise (per Coulter afterwards) call to the program. Coulter had made a speech days earlier in which she said, “I was going to have a few comments on the other Democratic presidential candidate John Edwards, but it turns out you have to go into rehab if you use the word ‘faggot’. Elizabeth Edwards confronted Coulter about the comment, as well as other comments Coulter has made accusing John Edwards of exploiting his son's death for political gain. Edwards asked Coulter to "stop the personal attacks" and accused her of "lowering the political dialogue" in America. Coulter responded that Edwards' complaints were an attempt to raise money for the presidential campaign, and questioned why the candidate himself was not making the call.
Matthews also caused controversy with remarks made off the air at a celebration of Hardball's 10-year anniversary in October 2007. He claimed that the Bush administration - specifically Vice President Cheney's office - has tried to "silence" him by pressuring MSNBC executives to put a stop to Matthews' criticism of the Iraq War. The White House declined to comment.
On May 15, 2008, he also had a confrontation with radio broadcaster Kevin James when he appeared on Hardball. At issue was a controversial speech made by President Bush in Israel, where he appeared to claim that statements made by United States Presidential Candidate Barack Obama were tantamount to Neville Chamberlain's actions of "Nazi Appeasement" in 1938.
The show was featured in the February 22, 2007 30 Rock episode "Hard Ball", in which series character Jenna Maroney came on the show to explain about how she was misquoted in the magazine "Maxim" about US military troops, but embarrassed herself even further when she confused Barack Obama with Osama bin Laden after she mentions whom she would support for US President in 2008.