The runtime supports Windows Server 2003, Windows XP, Windows 2000, NT4 SP6a and Windows ME/98. Windows 95 is not supported. Some parts of the framework do not work on all platforms - for example, ASP.NET is only supported on XP and Windows 2000/2003. Windows 98/ME cannot be used for development.

IIS is not supported on Windows XP Home Edition, and so cannot be used to host ASP.NET. However, the ASP.NET Web Matrix web server does run on XP Home.

The .NET Compact Framework is a version of the .NET Framework for mobile devices, running Windows CE or Windows Mobile.

The Mono project has a version of the .NET Framework that runs on Linux.