The recent approval of treatments for tardive dyskinesia (TD) has rekindled interest in this chronic and previously recalcitrant condition. A large proportion of patients with chronic mental illness suffer from various degrees of TD. Even the newer antipsychotics constitute a liability for TD, and their liberal prescription might lead to emergence of new TD in patient populations previously less exposed to antipsychotics, such as those with depression, bipolar disorder, autism, or even attention deficit hyperactivity disorder. The association of TD with activity limitations remains poorly understood. We review potential new avenues of assessing the functional sequelae of TD, such as the performance of instrumental activities of daily living, residential status, and employment outcomes. We identify several mediating aspects, including physical performance measures and cognition, that may represent links between TD and everyday performance, as well as potential treatment targets.