Virus scan in safe mode?

Is it best to run a virus scan on a PC in safe mode?
How about Ad Aware and Spybot?

I’m pretty sure Spybot and Ad-Aware won’t work in safe mode as it requires an installed windows service to be running to initialize. Or maybe that’s just the install process? Either way, if you have a really infected system, and you can get both to run, then yes, do it. I’d also consider running safe mode with networking to make sure you have the definitions updates for each program.