Trophic factors show great promise in laboratory studies as potential therapies for PD. However, multiple double-blind, clinical trials have failed to show benefits in comparison to a placebo control. This article will review the scientific rationale for testing trophic factors in PD, the results of the different clinical trials that have been performed to date, and the possible explanations for these failed outcomes. We will also consider future directions and the likelihood that trophic factors will become a viable therapy for patients with PD. © 2015 International Parkinson and Movement Disorder Society.