First, make sure the .NET Framework 3.5 is installed. If you already have it installed, first double check that its really the 3.5 version (4.0 and others aren't the same). Once you verify that you have it, then go to Programs and perform a Repair on it. Or uninstall/reinstall it. The .NET Framework can become corrupted causing strange issues with Centrafuse. 

If you have the .NET Framework 3.5 installed, first check this pre-requisite list to see if you're missing anything. Especially important for XP users. 

  1. Uninstall Centrafuse from Programs and Features (Add/Remove Programs in WinXP)
  2. When prompted, answer NO to saving your user settings. 
  3. (Optional) If you have maps installed, copy them to a different folder. Get ALL the map files (USARoads, etc)
  4. Delete the Centrafuse folder in: (usually) C:\Program Files\Centrafuse\Centrafuse Auto\
  5. Make sure you have ALL the pre-requisites installed. (see GET INSTALLER FILES link on your My Account page) 
    A: .NET Framework 3.5 (with SP1) (SP1 not required but recommended) - ( link )
    B: MS SQL Server Compact Framework 3.5 (usually installed with CF) - ( link )
  6. Check in Programs add/remove programs to see if it is installed
  7. Reboot and reinstall Centrafuse using the MSI (or EXE) installer. If you need to copy the maps back, or reinstall them do that now.

If you're still having issue, or are trying to run 4.1+ check out this helpful forum post:
http://forums.fluxmedia.net/general-centrafuse-questions/18345-centrafuse-installation-quick-start.html