Even as the first person to use force, it's possible to act in self-defense. If a reasonable person would think that physical harm is in the immediate offing, the defendant can typically use reasonable force to prevent the attack. People don't have to wait until they've actually been struck to act in self-defense. On the other hand, they can't use ostensibly preventative force without good reason.
(For more on defenses to crimes, see Defenses to Criminal Charges. For information on unreasonable use of force in potential self-defense scenarios, see Imperfect Self-Defense.)
Example: Attila and Genghis begin arguing after their cars collide. The argument gets heated, and Attila suddenly lifts his arm and forms his hand into a fist. Thinking that Attila is about to hit him, Genghis quickly knocks Attila to the ground and twists his arm behind his back. Under these circumstances, a reasonable person would think that Attila was about to hit Genghis. Because people don't have to wait to be hit before protecting themselves, Genghis acted in self-defense and isn't guilty of a crime. In fact, an officer could arrest Attila for assaulting Genghis (making Genghis fear that he was about to be hit.) (See Assault and Battery.)
Example: Popeye sees Bluto walking down the street. They've had a few scuffles in the past. Though Bluto is paying no attention to Popeye, Popeye has a hunch that his adversary may trip him when walking by. To prevent this, Popeye socks Bluto. Popeye doesn't have a valid self-defense claim, because the circumstances wouldn't suggest to a reasonable person that Bluto was about to attack him.