| From spaceflight terminology, the payload is the portion of the launch weight of a spacecraft which will be delivered to the destination or used to maintain crew and equipment destined there (orbit, another planet, what-have-you). This does not include the weight of the vehicle or its consumables, although it does include crew supplies such as food, oxygen, water, etc. etc. For example, APU reactants would not count as payload, since they are required to operate the spacecraft. Crew oxygen, however, might be - although it's a grey area, since you need crew to operate the spacecraft as well!
For the Space Shuttle, payload is generally the same as its useful cargo capacity. Many improvements have been made over the years (and continue to be made) which, by lightening the Shuttle or its components, allow more weight to be carried into orbit. Modifications to the External Tank after mission STS-5 allowed for an increase in payload of around 11,000 pounds, for no loss in performance.
Note that payload can usually be traded for mission performance, although it's usually not worth it - but if you need that extra 50 km of apogee, then maybe it's worth not bringing the astronomer. :-)
On unmanned flights, the payload is that part of the mission which will be delivered to orbit (for surface launches) or to another planetary orbit or surface (for deep space probes). | 
