The two biggest issues with using Plexi are A: scratching and B: static attraction. Plexi scratches much easier than glass when cleaning or transporting. It is also a major static attractant, so it sucks in all dust particles within a thousand yard radius, and the more you try and remove them, the better the static charge in the plexi gets built up, so it draws in three particles for every one you remove. I would say that plexi also seems to be more reflection prone, only because it is more flexible than glass so it is more likely to have subtle curves/bends in it in the frame, so it is harder to light it without having some kind of glare spot somewhere. That said, once you get above an 11x14 frame, Plexi starts to be the preferred option, and once you're above 20x24, it's almost the only option. Big frames bend and twist, and big glass doesn't. Applying the naturally occuring torque of a large picture frame to a plate of glass will make it shatter. To get glass thick enough that this doesn't happen, the weight of the glass is so great that it will rip the picture off the wall, and pull the frame apart.