Is energy really conserved? In high school I was taught energy was conserved. Then I learned that nuclear reactions allow energy to be converted into mass. Then I also heard that apparently energy can spontaneously appear in quantum mechanics. So, are there any other caveats with the conservation of energy?
 A: 
Then I learned that nuclear reactions allow energy to be converted into mass.

That would be the opposite and in any case, mass is energy (and energy is mass), so converting one into the other does conserve energy.

Then I also heard that apparently energy can spontaneously appear in quantum mechanics.

For a very short time, given by Heisenberg uncertainty principle. And that's not a violation of the conservation of energy.

So, are there any other caveats with the conservation of energy?

Why "other" ?  There's not any problem with the conservation of energy.
A: The topic of "Energy Conservation" really depends on the particular "theory", paradigm, that you're considering — and it can vary quite a lot.
A good hammer to use to hit this nail is Noether's Theorem: see, e.g., how it's applied in Classical Mechanics.
The same principle can be applied to all other theories in Physics, from Thermodynamics and Statistical Mechanics all the way up to General Relativity and Quantum Field Theory (and Gauge Theories).
Thus, the lesson to learn is that Energy is only conserved if there's translational time symmetry in the problem.
Which brings us to General Relativity: in several interesting cases in GR, it's simply impossible to properly define a "time" direction! Technically speaking, this would imply a certain global property (called "global hyperbolicity") which not all 4-dimensional spacetimes have. So, in general, Energy is not conserved in GR.
As for quantum effects, Energy is conserved in Quantum Field Theory (which is a superset of Quantum Mechanics, so to speak): although it's true that there can be fluctuations, these are bounded by the "uncertainty principle", and do not affect the application of Noether's Theorem in QFT.
So, the bottom line is that, even though energy is not conserved always, we can always understand what this non-conservation mean via Noether's Theorem. ;-)
A: Usually, but not always, Energy is a conserved quantity as the other answers have explained. 
But the following clarification is important: 
In the BB framework where space expands, or in the dual 'shrinking matter' (almost dual) (comoving framework), the ratio of matter/space is not invariant and energy is not conserved, i.e.  Nöether's Theorem does not apply. 
It is well known that photons lose energy as they propagate. I cannot find an argument to explain why particles should not also lose energy (as they are matter waves).  
The other relevant point is that energy can be destroyed, canceled, annihilated, as proved by experiment described here: real-live-antilaser, paper, and here a tentative discussion.  
Another example: what is the energy radiated by two dipoles centered in the same frequency and in phase opposition? It is zero. The same happens with two photons in similar conditions.
added:
It is well known that the cosmological redshift of light is usually interpreted(*) as a decrease in energy because the photons wavelength is increasing with time.  
The equations for the interference of parallel polarized light are:
see Kostya answer here and substituting Delta with Pi:
$\vec{E}=iE_{0}(cos(wt)+cos(wt+\pi))=0$ ; $I\vec{=|\vec{E|}^{2}}=0$.  
Light cancels when the instantaneous sum of the E and B vector field components equals 0, which is a fact long known (since Maxwell ?). (See superposition principle or interference.)
Another two situations that should make us think about our energy conservation assumptions:
accelerated charges radiate (discussion at matpages)
moving bodies in a gravitational field radiate gravitational waves (see MotionMountain free e-book, ch 18-Motion in General Relativity)
(*) I do not share the usual interpretation, but that one is the official.
I cannot remember of any other situation where energy is not conserved.
I'm not including possible Dark Energy issues (see CosmicVariance) 
Those four exceptional cases should make us think about our energy conservation concepts. 
A: Energy is always conserved without any caveat. 
With the advent of special relativity, mass and energy are considered equivalent. In other words, they are represented by a vectorial quantity called energy-momentum vector. Before relativity there were separate laws which have been unified.
It is a very fundamental law that is connected to some basic empirical properties of the universe, like the fact that the laws of physics do not change over time.
Energy cannot spontaneously appear in quantum mechanics -- however it cannot be precisely measured and this allows for energy fluctuations. The important difference is that although the total amount of energy can change, this is for very brief amount of time, after which the original quantity is restored. So the energy fluctuation can be considered virtual. You don't get energy out of nothing and energy is still conserved.
