To be honest, Dosbox--like any emulator--is never going to be the ideal solution. In my experience though, oddly the people who have the best experience with it are those who have experience tweaking actual DOS to get stuff working and aren't afraid to mess with settings and see what they do.

Tanooki mentioned joysticks not working right. I'll use that as an example--for some games, you need to adjust the dosbox .conf (which is editable via word processors, but on Windows Vista and 7 is initially hidden in some fucking buried subdirectory you're not likely to even know exists--I moved all mine to a C:\DOSBOXCONFS directory) so that timed intervals are either on or off (for most games, "off" is preferred) to make joysticks work properly. You also need to be fine with having multiple .confs and separate launch shortcuts for each, rather than expecting one conf to be a be-all end-all solution.

This sounds like a lot, but its exactly what PC gamers have always had to do since the days of MS-DOS and boot disks. You might almost call Dosbox the Y2K compliant version of old-school tweaking.

As for "games that simply will not work," I have never heard of one. I have heard, however, of games for which there is no "perfect configuration"--the Thor's Hammer Trilogy and Armed Tactical Fighters being two games that were mentioned on Ancient DOS Games as ones lacking any perfect configuration. I'm sure there are more.

In reality though, the main reason you want old hardware is for Windows 3.x/95/98 software titles rather than DOS, because there is no all-encompassing solution for those.