Parkinson’s disease (PD) has a prodromal phase during which non-motor clinical features as well as physiological abnormalities may be present. These pre-motor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta (SNc) involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies, like dopamine transporter imaging, currently offer the highest degree of accuracy for identifying pre-motor PD, but they are expensive as screening tools and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a pre-screening test, such as olfactory testing. This two-step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high-risk populations (e.g. patients with rapid eye movement behavior disorder (RBD) or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of pre-clinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large-scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease modifying therapy even before the development of evidence for dopamine deficiency.