Windows 3.x did not cohabitate well with certain games that required nearly the entire 640k of conventional memory to run. These are mainly games from the old DOS days; games that relied on DPMI were largely exempt. But to play certain Sierra titles, for instance, you had to set up one CONFIG.SYS configuration that loaded HIMEM.SYS and EMM386.EXE for Windows and another that left them out to free up that memory for your games. In later versions of DOS you could set up a menu to select the appropriate configuration at boot.

And of course IRQ diddling was still necessary to configure sound, network, and game controller hardware throughout the DOS era of gaming, which lasted well into the Windows 9x era.