Zotero is a very nifty little plug-in for Firefox that has very, very quickly become my reference manager of choice. It is in quite active development, and has a very promising future ahead of it, I think.
Pros: Web integration is insanely good! So you find the webpage for the latest article in Nature. A little icon appears in the browser's navigation bar. You click the icon, and all of the article's information - authors, abstract, direct URL, etc. - is dumped into your database. Zotero also accepts the standard "reference export" option, for sites that don't yet support direct export. Also, Zotero has two very functional plug-ins that allow users to "cite while you write" in Microsoft Word and OpenOffice.org Writer, and it functions in any operating system that supports Firefox. You don't have to be connected to the internet to use Zotero, either (because all files are stored locally).
Cons: The two biggest downsides that I've run into are 1) it is insanely difficult and not at all intuitive for the average user to create output styles in the current version, and the available output styles are quite limited (although they promise to correct this in the near future); and 2) character formatting (italics, underlining, etc.) is not an option within the database. Some journal homepages (notably JVP's BioOne page) aren't yet supported for direct linking. But. . .you can still import references using the standard "reference export" option (exactly as you do in Endnote).
Note: If you export from the BioOne website, use the Procite or Reference Manager format - the Endnote format doesn't seem to capture all relevant data. And BioOne, if you're listening, it's really, really annoying that you force the titles and author names of your reference exports into all caps. No journal on earth uses this format!
The Bottom Line: Zotero is *the* open source option for reference management, and it's only going to get better.