Hey Scott -- I run it all the time. First, you can use it as a fuel stabilizer so it never hurts to add it to your tank -- follow the directions for that.
I've done the Seafoam shock treatment to both 2 and 4 stroke motors and it works amazing. On my 350MAG I'd get dirty injectors every few years and the engine would miss and power would be off. Warm up the engine first. Full bottle of Seafoam into a 1 Gallon tank of fuel. Rig up a line to feed the engine the Seafoam treatment. Run the engine at 2000RPMs at the dock until you could hear it running rough. Shut off and let sit for 30 minutes -- start and repeat once more. Take boat for a hard run and no more dirty injectors.
Great for winterizing too -- get the spray can. Start the engine, let it warm up. Spray it into the carb with the engine running until you can get it to stall out. Remove plugs. Pour a small quantity into the cylinders. Turn over the engine with the plugs removed to distribute the product. Reinstall plugs. When you start the engine next season it will produce enough white smoke to kill every resident mosquito within 500 yards for about 5 minutes.
I also have a 4 stroke Ryobi weed wacker -- carb is so tiny on it that any dirt significantly impacts idle and starting. 4 screws to remove carb. Spray Seafoam over everything to clean. Reassemble and the thing will run great for a few more years.
Stuff can also be used in diesel engines -- added to the fuel or use it when changing fuel filters -- fill the filter with Seafoam to clean injectors.