From DesigningPatterns

Background

Microsoft ClickOnce is an application deployment framework. ClickOnce enables the user to install and run a Windows application by just clicking a link in a web page. The ClickOnce model supports two flavors of applications: installed applications (akin to conventional Windows applications with start menu integration) and online applications (browser hosted applications that are not installed, only run and cached).

.NET 3.5 SP1 includes several improvements for ClickOnce deployment of both Windows Forms and WPF applications. One of these improvements includes a FireFox browser extension to support Clickonce installations using FireFox browsers. See this Clickonce Firefox article. It looks like for Clickonce to work with Firefox, the client must have .NET 3.5 SP1 installed. Additionally, the client must be a Windows box. Alternatively, this blog post claims that recent versions of ClickOnce launched in Firefox should display in Internet Explorer.

ClickOnce probably requires a code signing certificate to verify the executable for clients ($200 - $500/year.) The wikipedia article mentions a possible caveat regarding certificate keys that supposedly should have been fixed in Visual Studio 2008.