Hi Tim,

I recently did some work with the YubiKey token for one-time password authentication in a multi-factor configuration; while smart cards do not require a multi-factor configuration, per se, you will at the very least likely need a custom authentication provider for authentication (I believe Mitchel Sellers has some great information on this topic).  The ease of implementation will heavily depend on how interoperable the smartcard vendor's back-end software is with .NET in general (for example, the RSA SecurID system was not very .NET friendly).

You will also experience potential issues with how DotNetNuke multiplexes its portals; many vendors supply software that aids in authenticating at the IIS level, and this is generally inappropriate for DotNetNuke installations hosting multiple portals (where IIS has no idea which user-portal binding is in play).  This is greatly simplified when only one portal is intended within a given installation.

Overall DotNetNuke can play very well with smartcard systems; the devil will be largely in the details, and in particular the card vendor.

Hope this gets you started!

Brandon