Most fish problems start with poor water quality. Even an infection is more likely in fish which are suffering in poor water.
As discussed in the Goldfish Care article, regular checks on the tank, equipment and water parameters are important, as are regular checks on the fish – does one seem listless compared to normal? Hanging at the top or bottom of the tank, swimming strangely or are their fins clamped?
A goldfish will lower its dorsal fin when it is swimming, but it should be fully extended when not moving quickly, likewise side fins kept close to the body, or a tail which is vertically narrower than normal can all be signs of an unhappy fish.
Some diseases such as Ich are easily spotted as the fish (usually all of them) develop an appearance of having been sprinkled with salt. Many diseases may show as obvious changes to the physical appearance of the fish, such as raised scales, lumps bumps or other strange growths. Other diseased may only initially show as a listless fish.
With details about your stocking level, water parameters, filtration, and some photographs or video, the folks over at goldfishresource.org will be happy to help you diagnose the problem.