What JoshGuru7 said.
First, you start with 1 hotbar. Click on the tiny icon to split a second, third, and fourth hotbar. That'll get you through the first few levels. You can reposition these anywhere on screen (and adjust to make them vertical or horizontal). Then drag skills, spells, action feats, equipment "clickies", potions, wands into the hotbars.
I also used the "key mapping" options to assign letter keys to certain hotbar spaces.
Once you get used to it, it becomes second nature. DDO has a huge variety of stuff that your character can use/activate. Just figure out what works for you and build up from there.