When do you say no?

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Have you ever been faced in a situation wherein you have to say no? For sure you have experienced such delimma. The negative thing for this situation is that, there are really times when you want to say no but it seems that you can't do it. Eventually, it'll end up that you have to do a thing that you don't wanna do...it all boils down to the fact that you don't know how to say no. I experience this situation sometimes; and I'm looking for some ideas as to how to say no in a nicer and a more creative way... Can you share some? Do you say no? When? How will you say it?