Turn off the furnace and air conditioning systems, so it doesn't start blowing at you as you work. Take off all vent covers and grills by unscrewing them from the walls and ceilings. They'll likely be dusty inside, so spread some newspaper around them first. Brush them off, then sponge them down with warm water and any nonabrasive household cleanser.
Put a piece of duct tape around the joints of the vaccuum hose, so there's no chance it will accidentally fall into the duct work. Using a brush attachment, vacuum all around the inside of the duct work, working in long side-by-side rows so you don't miss any part of it. Follow up by sponging out the inner walls of the duct work as far down as you can reach.
Any time you clean out the ducts, you should change the furnace filter. Note the size of your filter and get that size at your local home improvement store. Don't buy the cheapest, flimsiest filter you seek, but look for one that traps pollen and other small nasties in the air. Generally, the filter is installed just off the furnace box in the main trunk that delivers the heat to the house.