WordWeb Pro can look up words in virtually any program with just one click: just hold down the Ctrl key and right-click on the word. If you are online, with one extra click you can also search web references, for example Wikipedia. The hotkey can be customized, or you can use a keyboard shortcut if you prefer.
If you are editing a document you can select a synonym and replace the look-up word. WordWeb has the option to highlight widely used synonyms, great for helping you write clear easy-to-understand English.