Does ISA support two-factor authentication?
ISA 2004 and 2006 support multifactor authentication.
ISA increases security and deployment flexibility for Web application servers through enhanced multifactor authentication (smartcards, one-time passwords) , flexible integration with Active Directory (Lightweight Directory Access Protocol) , and customizable forms-based authentication for almost any Web application and client device.
ISA 2006 FAQ: https://www.microsoft.com/isaserver/prodinfo/faq.mspx