Listen to the request respectfully. Do not interrupt the speaker.
Phrase your "no" as simply as possible. Don't raise your voice or become upset, simply say that you cannot help this time. When you say no, say it in a confident, well modulated voice to sound more straightforward.
Don't feel obligated to explain. You have your reasons and they may not be ones you wish to discuss. If this is the case, try saying something like, "I'm just not able to." Leave it at that - if you must, change the subject, or say, "I'm sorry, but I need to go."
Explain simply, and only if you wish to do so. If the case really is one that you feel okay explaining, make your explanation as simple as possible.
Stand firm. If the requestor does not want to accept your answer, tell him or her that your mind is made up and that you will not change it.