1. To have all cylinders in an engine functioning. There's something wrong with my car—it's definitely not working on all cylinders.

2. By extension, to function or operate at the most desirable or greatest possible level of efficiency, speed, or productivity. (Usually used in the continuous tense.) The new website will be working on all cylinders once we get the comments section up and running! I only work on all cylinders after I've had my coffee.