This is a development release targeting (and requiring) Mac OS X 10.8 Mountain Lion and is 64-bit only (ie. it will only run on Macs capable of running 64-bit applications). The 4.0 stable series (currently at version 4.5.2) continues to be the recommended version for normal use, and is what you get by default if you hit the download page. On that same page you’ll find legacy versions that can be used with older versions of the operating system right back to Mac OS X 10.2 Jaguar.
A full changelog appears here. The version number has been bumped to 5.0a to indicate that this release breaks compatibility with older versions of the OS, and with 32-bit-only Macs. It includes some fairly radical changes to the internal plumbing and some aggressive cut-backs (eg. removing stale or incomplete localizations, removing the Growl support) in order to get onto the latest and greatest Apple technologies.
This will be a free upgrade for users with a valid license for Synergy 4.0 (which means any license purchased after 5 September 2006). See this blog post to find out whether you qualify. If you got Synergy through the MacHeist Giving Tree bundle see the MacHeist FAQ.