In order to exterminate all humans, one does not need to kill everyone directly. The task can be accomplished by separating humanity into separate breeding populations too small to be sustainable and too far apart for interbreeding to occur. The task can also be accomplished by destroying enough food sources for mass starvation to occur. Of course, people will feast on the flesh of the dead, so something must be done to ensure that the food sources are not replenished or replaced. Humans could also be destroyed if they were to be replaced by some other organism or their habitat were destroyed.
Many of the extermination methods here require a mop-up effort. This would have to be done by a suicide cult or some non-human force such as giant robots bent on world domination, or Daleks, who by definition want to kill everyone.
At the moment, if any nation decides to use nuclear arms in aggression, nations allied with the victim are likely to use their nukes in revenge, which will cause the allies of the initiator to use their arms, and so on in a chain reaction. Existing nuclear stockpiles are sufficient to destroy most or all human life if used in a manner that will throw enough dust into the air to cause a nuclear winter or if population centers are carpet-bombed. Bomb placement can be adjusted so that the prevailing winds will carry fallout over more population, forcing it to leave or die. Carpet bombing will probably also result in enough dust and debris in the air to cause climate change such as nuclear winter. Some humans have access to facilities suitable for surviving these conditions. In order for the extermination to be successful, we would have to deal with these small population islands, either by hunting and killing them, providing them insufficient warning, ensuring that they are too damn small, or destroying their survival facilities beforehand.
A suitably virulent disease has the potential to exterminate all humans. However, few easily-transmitted diseases - human or plant - have a 100% mortality rate. For this disease or set of diseases to wipe clean the earth, it would have to kill all humans or kill all human food sources (or fragment the population) - not an easy task. Sufficient technology and genetic diversity exists to make this a difficult proposition. Genetic engineering can either significantly reduce this diversity (as bad selective breeding and made-to-order organisms can do) or significantly increase this diversity (as a frozen zoo, well-implemented selected breeding, and made-to-order organisms can do). Genetic engineering also allows the design of diseases that will not survive in nature - ones that kill their host populations at an unsustainable rate.
Death from space is suitable to exterminate all humans, as all humans live on one planet. If an object with sufficient kinetic energy can be aimed at the earth, it could cause the equivalent of nuclear winter or could smash the planet into many tiny bits. Humans have a better chance of surviving nuclear winter and/or a large asteroid impact than they are of surviving a collision with a rogue planet or something else big and fast enough to destroy the surface.
Certain fun physics can also destroy the earth. With sufficient technology and energy one kilogram black hole could be created. If this hole is dropped into the earth, all life is fucked because the singularity because over a period of a few years the earth will be absorbed. Luck or technology could save the collective ass of the planet - inbound matter could form or be formed a rigid sphere around the singularity, part or all of the planet's mass can be accelerated to orbital velocity (to orbit the hole), the hole can be caught and allowed to evaporate, or the hole could be too damn small (less than one kilogram would probably have to be used).
Humans can be replaced by another species. The oceans provide an environment relatively unaccessable to humans where life can evolve nearly free of interference. Certain species of squid and octopus show intellegence that could be cultivated, and an octopus has the ability to manipulate objects, which, with some development could (or may already have) be put to use in making and using tools. Another source of a replacement species is humans themselves. For these arguments, we will define human to refer to a member of the species homo sapiens. If a sustainable population is split off from the rest of humanity for long enough (the fewer the diffirent selection pressures, the longer it will take), they will eventually become a separate species incapable of interbreeding with homo sapiens. By definition they will no longer be human. The final source of a replacement dosen't even require a split population. Given enough time, even a single interbreeding population of humans will drift and eventually become incapable of interbreeding with the humans of today, and by definition will be another species - and if an intellectual cacaclysm occurs between then and now, these future people will look at the archeological record and decide that we were a separate technologically advanced species from which they evolved. So, given that humans aren't killed by these other methods, your distant children will exterminate all humans!