Buy a fresh supply of natural sand each year. This tan, sterilized sand is sold at your local gardening/hardware store.
Keep your sandbox in a sunny area, the sun kills microorganisms!
Get in the habit of checking the sandbox weekly with a screen or sifter for animal droppings or unwanted contents such as rocks and glass.
If your sandbox is a portable one (such as the turtle shaped one), store in your basement or garage over the winter. The cold weather could cause the plastic to warp or crack.