I have a Wacom Intuos PTZ-631W. The mouse and pen sometimes stop responding and I can't even open the properties dialog box (using a separate Logitech RF mouse) when this occurs. Wacom has already replaced the RF mouse but - while the situation improved - the tablet still doesn't respond on occasion.

SOURCE: My Wacom Intuos3 tablet won't switch into pen mode

I had the same problem with my Intuos3 on Vista. Tech support suggested the following.

Do this.....Go to Start--->control panel---->system(in classic view)---->device manager--->click on "human interface devices"--->then click on "Wacom virtual HID driver" and right click on that and disable it. Your computer will ask you to restart and you will want to do that.

Everything works fine now.

SOURCE: serial to usb wacom tablet problem

I just got Vista and it killed my Intuos2 w/serial to usb also, but here's a half solution:
Download Wacom driver 4.78-6 http://www.wacom-europe.com/int/downloads/driver/driver.asp?lang=en. Make sure you remove any other Wacom drivers, tablet, and reboot. Install 4.78-6 driver and select serial port when the choice pops up. Plug in your tablet with the serial to usb adapter, wait a few seconds and click retry. Complete the install and reboot.
Your Wacom tracking should work now, but certain things might not work like pressure sensitivity and you'll get annoying error "reinstall driver" pop-ups.

I think you can aslo buy a PCI-serial card for your computer and skip the serial-usb adapter since Vista doesn't support the adapter for Wacom tablets.. but I'm not sure if there's a working Vista serial Wacom driver either.. or ever will be. The age of XP and Legacy support is at an end my friends.

SOURCE: Wacom pen not working - on the pen side

check the battery of the pen

SOURCE: My Wacom Intuos3 tablet won't switch into pen mode

The winning answer came courtesy of Mr Benedikt Schmitt of Wacom Europe, who offered the following solution: from the Windows Device Manager, disable the “Wacom Virtual Hid Driver” device. (Go to Control Panel > System and Maintenance > Device Manager, find the driver, right-click it and choose “Disable”.) One reboot later (welcome to Windows-land, circa 2008?), everything works as desired. Pressure and tilt sensitivity inside Photoshop still work, and the pen functions just fine in the rest of the Windows desktop. The absolute mapping makes it an absolute pleasure to point quickly and precisely. It makes my laser mouse feel rather clumsy navigating a large 24′ screen!

SOURCE: Wacom Intuos 3 unintentional double click

I had the same problem. I went here: http://www.beeldbuijs.nl/solutions/hardware/scrollwheel_adjustment.htm, followed the directions (only 1 screw on the bottom in the back for the Intuos 3), cleaned out the dust, works fine (for now)