Substantia nigra (SN) hyperechogenicity has been proved to be a characteristic finding for idiopathic Parkinson's disease (PD), occurring in more than 90% of the patients. This echofeature is owed to increased amounts of iron in the SN region and reflects a functional impairment of the nigrostriatal dopaminergic system. In a prospective blinded study in which a group of patients with early mild signs and symptoms of unclear Parkinsonism were followed until a definite clinical diagnosis of PD, the hyperechogenicity of the SN was demonstrated to be highly predictive of a final diagnosis of PD. For the diagnosis of PD in individuals with early motor symptoms, both the sensitivity and positive predictive value of SN hyperechogenicity were higher than 90% and both the specificity and negative predictive value were higher than 80%. For early differential diagnosis between PD and atypical Parkinsonian syndromes, the sensitivity and positive predictive value of SN hyperechogenicity were higher than 90%, and both the specificity and negative predictive value were higher than 80%. The diagnostic specificity is increased if combining the TCS findings of SN, lenticular nucleus and third ventricle. In asymptomatic adult subjects, SN hyperechogenicity, at least unilaterally, indicates a subclinical functional insufficiency of the nigrostriatal dopaminergic system. Recent papers revealed that SN hyperechogenicity might suggest preclinical PD. Reduced echogenicity of midbrain raphe indicates increased risk of depression in PD patients. Caudate nucleus hyperechogenicity has been associated with drug-induced psychosis, and frontal horn dilatation >20 mm with dementia. Transcranial brain sonography can be a valuable tool for managing patients with Parkinsonian signs and symptoms.