Individual extragalactic dark matter halos, such as those associated with nearby galaxies and galaxy clusters, are promising targets for searches for gamma rays from dark matter annihilation. We review the predictions for the annihilation flux from individual halos, focusing on the effect of current uncertainties in the concentration-mass relation and the contribution from halo substructure, and also estimating the intrinsic halo-to-halo scatter expected. After careful consideration of recent simulation results, we conclude that the concentrations of the smallest halos, while well-determined at high redshift, are still uncertain by a factor of 4-6 when extrapolated to low redshift. This in turn produces up to two orders of magnitude uncertainty in the predicted annihilation flux for any halo mass above this scale. Substructure evolution, the small-scale cutoff to the power spectrum, cosmology, and baryonic effects all introduce smaller, though cumulative, uncertainties. We then consider intrinsic variations from halo to halo. These arise from variations in concentration and substructure, leading to a scatter of ∼2.5 in the predicted annihilation luminosity. Finally, we consider the problem of detecting gamma rays from annihilation, given the expected contributions from other sources. We estimate the signal-to-noise ratio for gamma-ray detection as a function of halo mass, assuming that the isotropic gamma-ray background and cosmic rays from star formation are the main noise sources in the detection. This calculation suggests that groupscale halos, individually or in stacks, may be a particularly interesting target for the next generation of annihilation searches.