I think the difference with Frontline Plus is that it kills the eggs as well whereas Frontline just kills the fleas. It works by going into the cat`s oil glands and spreading around the skin. I don`t know anything about the other brands but I think they actually go into the cat`s bloodstream. When someone who isn`t a vet applies systemic drugs themselves, there is always a chance they won`t do it that efficently (that has happened with farmers administering drugs to their animals). Next thing you know, you`ve got drug resistent bugs. If Frontline doesn`t work, it`s probably because it`s quite difficult to get the whole lot onto the skin and not the fur. When that happens, the cat doesn`t get the full dose.