I have no problem with this subject being in the game (core, later book, or whatever). I think (and would handle in my game as such) that the powder would be much more common in forms and uses outside of muskets/firearms. Cannons, maybe. Fireworks, sure! Explosives, occasionally. After all, it is not exactly an advanced, technological substance at heart.
Guns, however, are a different story. People have already noted thier inaccuracy and unreliable nature. Also, keep in mind that interchangable parts were not used until the 18th century (maybe 19th?). So, anytime a gun needs to be repaired....off to an expert for major work! Typically, this would mean that each time it misfired (or even fired correctly!) there was a chance that it needed repairs. To say nothing at all of falling. Finally, unless the DM allows the use of 19th century smokeless powders, the guns would require extensive and regular cleanings (far more than typical D&D weapons' maintenance) or the residue from the gunpowder would literally corrode the insides of the barrels of the gun.
Gunpowder/blackpowder (blackpowder would be most appropriate for this era) poses its own problems. Manufacture of it was dangerous, storage and transportation was risky, and large quantities had to be used to make it effective. Oh...and nearly half of the mass of the powder is wasted in any explosion of it, resulting in an inefficient blast accompanied by a LOT (did I stress the word LOT enough?) of thick, black smoke. Only if the DM wanted to allow 14th century technology would users benefit from advances that allowed the luxury of granulated blackpowder, slightly reducing the risk of spontaneous combustion via static electricity, and faster/easier/safer manipulation of the powder into what it was actually going to be used for.
So....all in all....I would like to see it in the PHB as an alchemical item for use as diversions, flash-bang distractions, and hints of use in more advanced forms. Certainly would not be a common substance, and absolutely nothing you'd want to carry if you expected trouble with red dragons or fireballs. In game terms, I'd judge that its extremely dangerous nature would cause a BAD explosion on a critical failure of whatever skill is used. (Then again....if beholders have to blast multiple times with a Flshe to Stone ray for you to finally become petrified....it sounds as if dire concequences are not "in theme" with D&D4E)