We prove that deciding if a diagram of the unknot can be untangled using at most k Reidemeister moves (where k is part of the input) is NP-hard. We also prove that several natural questions regarding links in the 3-sphere are NP-hard, including detecting whether a link contains a trivial sublink with n components, computing the unlinking number of a link, and computing a variety of link invariants related to four-dimensional topology (such as the 4-ball Euler characteristic, the slicing number, and the 4-dimensional clasp number).