As far as your application is concerned, "open with" will be the same as if you double clicked on a document in explorer and it went straight to your application.
Unless you are doing something fancy, then you don't need to worry about this - MFC will do the heavy lifting for you.
If you do care for some reason... Explorer will look in the registry, and find out how to call your application. It will either be "myapp.exe somefile.file", or use DDE to "tell" your application which document to load.
In both cases, MFC will just create a new instance of yoour program, which creates a new view / document as speficied in the CxxxDocTempplates then load the document using the documents OnOpenDocument method, or serialisation if you've left the open / saving alone.
An example of reasons to care about this is given by the article
Limiting an application to a single Instance - the MFC way[
^]
In short: MFC means you don't have to care, unless you are doing something out of the normal.
Iain.