We'd love to help you find the answer 
This is not going to work on all Macs, but should, along with the recent Frostwire 5 series, present no problems with Intel 64 Bit Machines running the latest updated of OS X 10.5.x and 10.6.x
Let us know how it works for you.
if you have Mac OS X 10.4.11 you can run Frostwire 4.21.1 but the Torrent client will not work, so Frostwire 4.18.6 might be the version to go for.
If either does not connect, see Replacement of gnutella.net file. This will most likely require replacing, in order for Frostwire to connect. Open Frostwire and allow it to load, and then close it fully, before attempting to do this
If You have Mac OS X 10.3.9 Please see Frostwire 4.10.9 for Mac OSX 10.3.9 and earier
If You have OS X 10.5.x or 10.6.x and have problems with Frostwire 4.21.3 :
Please go to Applications > Utilities > Java and possibly a folder Java 6 or 1.6 find and open Java Preferences and check that at the top Java 6 is selected and underneath J2SE 6 is top of the list ..drag it if necessary. If your software updates are up to date, and there is no sign of J2SE 6 then I suspect you are using 32 bit.
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I have found that Java J2SE 6 update to 1.6.0_22 is only for Leopard users with 64-bit capable Intel-based Macs. From what I can make out, if you Have a PPC machine OR intel 32 Bit then it will not apparently work. I must check further, and meanwhile suggest you downgrade to Frostwire 4.21.1. If you do this please let us know how you get on and in particular whether the Torrent side works.
EDIT: To find out, for sure, if your Intel machine is 32 or 64 bit visit http://support.apple.com/kb/ht3696
