If a coworker was bothering you, how would you handle it?

When in the workplace, we deal with all kinds of people with different attitudes, backgrounds and spiritual energies. People may offend others and not be aware or not even mean any harm. If one of your coworkers is really annoying you or is offending you in any way, how would you handle the situation? Would you be discreet and confront the coworker privately to sort things out and clear up any misunderstandings or would you tell anyone who would listen? I would prefer to handle things discreetly with a private confrontation (this does not work all the time). How would YOU handle this? Please...no rude or sarcastic answers. Thanks.