We characterize the local single-valuedness and continuity of multifunctions (set-valued mappings) in terms of their premonotonicity and lower semicontinuity. This result completes the well-known fact that lower semicontinuous, monotone multifunctions are single-valued and continuous. We also show that a multifunction is actually a Lipschitz single-valued mapping if and only if it is premonotone and has a generalized Lipschitz property called Aubin continuity. The possible single-valuedness and continuity of multifunctions is at the heart of some of the most fundamental issues in variational analysis and its application to optimization. We investigate the impact of our characterizations on several of these issues; discovering exactly when certain generalized subderivatives can be identified with classical derivatives, and determining precisely when solutions to generalized variational inequalities are locally unique and Lipschitz continuous. As an application of our results involving generalized variational inequalities, we characterize when the Karush–Kuhn–Tucker pairs associated with a parameterized optimization problem are locally unique and Lipschitz continuous.