Customizing through CSS rules is a straightforward but powerful method for changing UI in CONTENTdm. The responsive Website Configuration Tool lets you upload a CSS file to the Global Settings > Custom > Custom CSS dialog and also an individual CSS file for each collection to the Collection-level Settings > Custom > Custom CSS dialog. In all cases, you can only upload a single CSS file so all of your CSS for each context will need to be placed into one file.
If you upload your CSS file at the global level it will affect all pages in CONTENTdm. If you choose also to upload CSS for one (or more) specific collections, that CSS will apply only when the page context is specific to that collection (landing pages, item pages, search/browse page for a single collection).
To make CSS customizations easier, there are a number of standardized class names available in the markup of the CONTENTdm pages. These classes will not change as CONTENTdm is updated in the future so can be relied upon for upgrade-proof custom styling.