A number of independent studies provide evidence that transcranial sonography (TCS) is helpful in the diagnosis of idiopathic and monogenetic Parkinson's disease (PD). In the clinical setting, it may exclude a number of secondary or atypical parkinsonian syndromes at very early stages. TCS may additionally depict morphological alterations of symptoms associated with PD motor features like midline alterations in PD-associated depression. Importantly, substantia nigra (SN) hyperechogenicity, the typical ultrasound marker of PD, can also be found in approximately 9% of healthy subjects. PET studies and conditions challenging the dopaminergic system indicate that this stable ultrasound feature has a functional relevance. Ongoing longitudinal studies test the hypothesis that SN hyperechogenicity is a risk marker for nigrostriatal vulnerability.