I had some trouble with Spotify URIs on Google Chrome, seeing as it uses xdg-open for everything external (not a bad thing) and I could not use about:config as with Firefox. After some googling and asking around I found this to work:
Note that I’m running GNOME, so this guide covers the use of gnome-open. If you use KDE, Xfce or any other desktop environment, and you know how to add support for other URIs on that version of xdg-open, feel free to comment.
First, we need a bash script to run Spotify. This one assumes that you’ve installed Spotify with PlayOnLinux:
#!/bin/bash cd "$HOME/.PlayOnLinux/wineprefix/Spotify/drive_c/Program Files/Spotify" WINEPREFIX=$HOME/.PlayOnLinux/wineprefix/Spotify/ wine spotify.exe /uri $1
Save this and make it executable with chmod +x.
Now, let’s tell GConf that we have a URI handler for spotify.
gconftool-2 -t string -s /desktop/gnome/url-handlers/spotify/command "location of the bash script %s" gconftool-2 -t bool -s /desktop/gnome/url-handlers/spotify/needs_terminal false gconftool-2 -t bool -s /desktop/gnome/url-handlers/spotify/enabled true
After that, you’re done! Enjoy launching Spotify directly from Chrome/xdg-open!
Thanks to:

watch for the typo on the last gconftool-2 command, it should read:
gconftool-2 -t bool -s /desktop/gnome/url-handlers/spotify/enabled true
Comment by Ben — October 7th, 2009
Thanks, I was wondering why it didn’t work on my other computer..
Comment by TheLinx — October 11th, 2009
I was so very glad if anyone would found a solution to do that in kde.
Comment by Bausparfuchs — March 10th, 2010