Usually the shorter the weapon is, the harder it is to use it. (Naturally I am speaking of impact/cutting weapons.) First, the modality of fighting is rather wide for the knife. To be competent, you cannot skip out on learning striking and arms' length grappling. Second, the inherent nature of fighting with a knife is not pleasant. You are also in very close, and the knife is a very fluid, fast weapon. That means if your opponent is armed with the same, you're likely to end up with a lot of gashes even if you win. If you have trained enough, you'll know that dropping your knife is a real possibility. Third, it takes a lot longer to get good with the knife than with a longer, more powerful weapon. The disparity is so big that at times you might wonder why you even train in it when you can just take a better weapon and be a lot more lethal. If you have to choose between a knife and a machete, grab the machete. If you have to choose between a machete and a sword, grab the sword.

I wouldn't recommend relying on the knife for defense unless you've gotten quite a bit of training; i.e., much more than a weekend seminar, like a few years at the least, preferably several years or more. Filipino and Indonesian arts are typically where you'd want to go. You also have to keep up your skills by constant training. Then you hope to God that if you end up having to defend yourself, you don't find yourself having brought a knife to a gun fight. The machismo factor is often what makes people talk about the knife.

There is a lot of misinformation out there, even if only indirectly. Recently there was someone advertising steel plates for flak jackets (or something like that). The manufacturer's website says their product will also defend against the knife. I guess they were thinking of the dreaded "stab" that you hear so much in the news, such as: "There was a stabbing last night!" (by an idiot who doesn't know how to fight with the knife). If you take a look at that jacket, it conveniently exposes the areas with major blood vessels. These are some of the prime targets for the knife, and in fact the jacket make these areas more visible. Thank you for wearing the vest. Now there are guiding lines for me, and you're bulky and slow.

I don't think it's a good idea to discuss actual self defense situations on a public forum.