Recent research has indicated that consumers of upper limb prostheses desire lighter-weight, anthropomorphic devices. The potential of dielectric elastomer (DE) actuators to better meet the design priorities of prosthesis users is explored. Current challenges are critically reviewed with respect to (1) durability, (2) precision control, (3) energy consumption, and (4) anthropomorphic implementation. The key points arising from the literature review are illustrated with empirical examples of the strain performance and durability of one of the most popular DEs, VHB 4910. Practical application of DE actuators in powered upper extremity prosthetics is at present impeded by poor durability and susceptibility to air-borne contaminants, unreliable control owing to viscoelasticity, hysteresis, stress relaxation and creep mechanisms, high voltage requirements, and insufficient stress and strain performance within the confines of anthropomorphic size, weight, and function. Our review suggests that the implementation of DE actuators in powered upper extremity prosthetics is not feasible at present but worthy of reevaluation as the materials advance.