Originally posted by RogueJSK:
As long as the dot is properly zeroed, you simply place the visible red dot on what you want to hit and press the trigger. The dot doesn't need to be centered, or lined up with the sights.
The sights are there as a backup. You should be looking over the top of the iron sights at the red dot floating in the optic's "window".
For example, in the below image, the shot should impact on the target's upper lip, even though the red dot isn't centered, and the iron sights aren't aligned.
However, as you're first getting used to the red dot, some people find it to be helpful to draw and present the handgun as you normally would, lining up the sights in the process, as an aid to learning to rapidly acquire the red dot. But with time and practice, you will transition to picking up the red dot without using the sights as a crutch.
And some folks are able to start training right away with just the red dot, without relying on the iron sights at the beginning. A proper, repeatable grip/draw/stance helps with this.