A NFL coach may challenge a call during a game by throwing a red flag onto the field. This indicates to the officiating crew that the coach feels there may be sufficient evidence to overturn a call. In order to ensure that challenges don't get out of hand, the NFL has set restrictions on how often challenges can be made.
A coach may throw a challenge flag at any point except for after the two-minute warning of either the first or the second half or overtime. A coach may only challenge twice per game. However, if both challenges are upheld, he receives a third challenge.
To challenge a play, a coach must throw his challenge flag before the next snap. If he fails to challenge before then, the play stands as originally called. Coaches must choose if they want to risk challenging a play, as making a challenge that is not upheld costs a team a timeout. A coach who does not have at least one timeout may not challenge a play. In order to overturn a play as it was called on the field, a referee must see indisputable evidence on a replay that proves that the play was not correctly called.