Clinical trials in Parkinson's disease (PD) have focused in two major areas: treatments designed to alleviate signs and symptoms in the short run, and treatments designed to modify the long-term progression of the illness. In clinical trials of short-term improvement with early PD patients the most common primary outcome measure is the Unified Parkinson's Disease Rating Scale (UPDRS). Motoric dysfunction, loss of ambulatory capability, cognitive impairment, mood disruption, and autonomic dysfunction all eventually contribute to potentially severe disability in individuals with advanced PD. Trials are just emerging that focus on the development of overall disability in PD, rather than measuring impairments in any particular domain such as motor function or cognitive impairment. Multiple trial designs have been proposed and used in studies to assess disease modification in PD. Several particular safety concerns have emerged in the context of PD clinical trials.