It took me about 9 or 10 months. When I developed a severe flare, my rheumy started me on prednisone and plaquenil at the same time. This way while I tapered off the pred over 8 months, the plaquenil was building up in my system. Once I stopped the pred, I got some fatigue back and felt a little flarish, but nothing like i was. Then it took several more weeks just on the plaquenil before I really noticed I was feeling pretty good. I take 400 mg per day of the plaquenil. I had have some little flare-ups while on it but they didnt last long and were not as bad as before I ever took it. The only time I flared up badly was when my epidural steroid injections into my spine wore off. But even then, it only took about 3 weeks for me to feel better. It can work so slowly that it's hard to notice it's giving you any benefits. But it sure helps me keep flares from going berserk.