Roger my experiences have all been with Lightroom but the overall principles are much the same across other DAM applications.
In Lightroom the core of the application is a SQLite database.
The database stores information about the image collection including metadata, keywords, editing instructions, etc, and the image's location.
Images are NOT stored directly in the database but the pointers pointing to the location of the images are.
There is no reason why images cannot be stored across multiple internal and external hard drives. (I and many others do this).
Obviously if an external hard drive is offline then Lightroom cannot directly access those images but it still knows where they should be. Bringing that external HD back on line instantaneously makes those images available again.
The terminology used in Lightroom calls the database a catalog.
In principle only one catalog is required.
Many individuals citing organizational needs or performance issues break their image collections into multiple catalogs.
If you do this then know that you are creating a rod for your own back.
It is far better to keep everything in one catalog so the entire collection is instantaneously accessible and searchable.
Back up the catalog religiously.
To repeat the catalog is not your image files it is the database.
Backing up the database regularly means that you have a very recent fallback should your catalog become corrupted.
You can also backup the catalog to multiple physical locations as well.
Murphy's law of computing tells you that database corruption is inevitable sooner of later.
In Lightroom there is the ability to optimise the catalog.
This helps immensely with performance as the image collection grows.
Back up you images.
Create an online backup of all your images files exactly as they are in your primary storage HD.
Create two redundant offline backups of your images again with the folder structures exactly as they are on your primary storage HD.
You will also ideally need two remotely located archives of your image collection that are also updated regularly.
The recommendation here is to use HD's that can store the entire collection on one drive and then obviously to duplicate that.
If you have been following this then you will see that in fact one ends up with multiple backups of both the database and the actual image files.
The fact that a single catalog (database) is the primary organizational tool in no way implies susceptibility to data loss as long as the precautions mentioned above are taken.
I can easily accomplish these tasks using Lightroom but other applications that are truly DAM capable should give the same overall utility.
There are several resources that I would like to recommend to you:
Peter Krogh, The DAM book. (the definitive overview of DAM);
Seth Resnick, D65's Lightroom 4 Workbook: Workflow, Not Workslow in Lightroom 4. (DAM at work with Lr4) and;
Luminous Landscape Guide to Asset Management 'Where the #%*! Are My Pictures?' with Seth Resnick and Michael Reichman http://www.luminous-landscape.com/videos/wamp.shtml
(the best of the lot to get you started practically).
Feel free to sharpen up the questions as you get going in your quest.