The End of Humanity: Could the Human Species Destroy Itself?
There are lots of ways humanity could be wiped out - although I don't think any of them are particularly likely.
Natural causes - An extinction-level asteroid impact would probably be sufficient, although not much else would - a disease epidemic, major climate shift, etc. would still leave many survivors to rebuild within a few hundred years. The window for such an impact is, however, extremely short, because it's extremely likely that within 300 years or so we will have the means to predict and avert all dangerous impacts. And the chance of that happening is, from historical comparison, 0.001% or less.
There are a few other possibilities that would be much more catastrophic, though. One is a supernova very nearby, which would blast Earth with intense gamma radiation and most likely kill all macro-organisms. However, there aren't any stars large and old enough for this to be a risk for hundreds of thousands of years. Another is orbital destabilization of Earth (such as ejection from the Solar System) by a close-passing star - but the chance of that is extremely remote, and in addition we'd have thousands of years of warning. And the last that I can think of is alien invasion… which is really out there, obviously.
The eventual solar threats to life on Earth are not really relevant to humanity/posthumanity. The Sun is not large enough to supernova, but it will eventually engulf the Earth when it runs out of internal fuel and swells into a red giant. That's a good 4-5 billion years away, but well before that, though, the Sun will have become bright enough to heat Earth's surface enough to trigger a major atmospheric shift by overwhelming the "cloud effect" (which keeps temperatures on Earth stable) with a runaway greenhouse gas effect, boiling the oceans and making the planet Venus-like, uninhabitable except by micro-organisms. But even that is about 2 billion years away, plenty of time for posthumanity to rise and either avert the problem or simply head elsewhere.
Accident - A scientific experiment run awry, or an unexpected side-effect of some new technology could potentially wreck some serious havoc.
One possible horribly catastrophic scenario would be the unforeseen generation of a miniature black hole somewhere on Earth. If the hole did not evaporate instantaneously (and it would have to be pretty large not to, so I don't know how it would be possible to generate one accidentally) it would quickly bore a hole to the center of the Earth, absorbing more and more mass as it went, and eventually implode the planet. But that evaporation problem is pretty severe, although if Hawking was wrong about BH radiation (as it hasn't been experimentally verified) it would be a lot easier. Furthermore, sufficiently far into the future, the destruction of the planet would not necessarily mean the destruction of the posthuman species.
A more peculiar possibility is the creation of a new type of "transforming" matter - for example, a supercollider experiment might generate some bizarre particle which transforms every particle it comes in contact to a bizarre particle as well - so the number of bizarre particles grows exponentially, eventually transforming the whole planet. Whether or not this is even possible… who knows, it's just speculation.
The last one I've heard talked about is the nanomachine-gone-berserk. If in the future we create a race of benevolent nanobots (to do things like repair cellular damage, make chemical and material compounds, enhance performance of macro-organisms, etc.) and allow them to self-reproduce (to increase efficiency) there is a possibility that some sort of mutation could create a disease-like strain of nanobot which instead of benefiting its hosts acted like a disease and transformed all material it incorporated into more malevolent nanobots. But, I think this is quite unlikely, because any self-reproducing machines would be loaded with thousands of preventative measures to avoid viral behavior, and furthermore in the event of an epidemic civilization could devise - or evolve - an "immune system" to counter this. A deliberately weaponized version of nanobot to be as virulent as possible (that escapes from the lab or looses its restrictions) might be more dangerous, but there would still - probably - be sufficient safeguards and countermeasures. It all depends on how hard it is to produce them.
Deliberately - The scenarios by which humanity could wipe itself out by choice are mostly the same as those above, except instead of the disaster being accidental, it would be instigated by some sort of apocalyptic cult. I am not sure how likely this is - personally I expect that technology by which a central government can actively track the activities (and even thoughts) of everyone and every thing alive will precede any of the above technologies and stop this long before it starts, and the social institutions which produce this sort of destructive behavior (extremist religion) will be filtered away, so I would say that the chance is extremely remote.
There is also the possibility that civilization could simply decide that Earth would be better off without a posthumanity, and eliminate itself. But I don't see it happening.
Collateral damage - The only example of this I can think of is a war that got out of control due to the use of weapons of mass destruction - either the ones we have now (nuclear weapons) or those of the future (engineered pathogens or nanobots?). However, this possibility is dependent on the existence of two or more large antagonistic nations armed with the capability to research and mass-produce these weapons… a situation I don't think is likely to be the case for very long. This will remain a risk for maybe a few hundred years, but I'm convinced that eventually cultural homogenation and advancement will inevitably lead to world government, and large-scale war will be a thing of the past.