Re-parsing the answers, I think I found the combining element of at least 2 previous answers is the problem of breaking the barrier between syntax and semantic. Which is the problem actually every programmer and computer scientist is working on. (Lately "semantic" is increasingly appearing as topic of whole CS-areas.) Most of the fields and topics we have opened up start with the promise to break this barrier. Up to now all of them sooner or later they reduced from "creating intelligence" to "intelligent algorithms".
AI is probably the research area where this has been most prominent, but in the end, many other people have been dreaming of what is basically a "Do what I mean"-button. (I could fit in the evolutionary algorithms, neural networks, and lately the semantic web-people in here.)The main hindrance being that everything a computer does is shifting bits.
I am probably spreading prejustice and foolery here, because for materialists this is not a fundamental problem, because shifting bits is probably all we are doing in the human brain. It simply might be a problem of complexity.
Well... I am not willing to start that discussion here, and besides syntax vs. semantics is a quite general topic. Spending too much time on this definitely keeps one from solving some of the more specific problems mentioned in other answers. Tackling these is much more effective but it helps to keep in mind that there are very fundamental barriers here, that we are not (yet) able to break through.