For me it's when the game shows any weird behaviour (wrong sprites being drawn, graphical glitches, wrong sounds being played, errors that don't make sense, etc...), and ALWAYS before building an executable, especially if I'm building using the YYC. If you're making a game for HTML5, I would definitely recommend clearing it before building a test after adding any new GFX or SFX as the HTML5 target seems to be much more sensitive to changes in the cache.