Accurate diagnosis of Parkinson’s and other degenerative parkinsonian syndromes is important for management and prognostic purposes. Diagnosis can be challenging in early disease and in atypical cases. This chapter focuses on the application of magnetic resonance imaging (MRI) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) in degenerative parkinsonism and related disorders. For Parkinson’s disease (PD) and related conditions, conventional MRI is not diagnostic, but it can be useful to distinguish PD from other atypical parkinsonism. The new developments in the field utilizing T1-weighted structural MRI, iron-sensitive MRI, diffusion-weighted imaging (DWI), and resting-state fMRI (rs-fMRI) have shed light on the underlying pathophysiology of PD. They may also hold promise as both diagnostic and prognostic biomarkers. The use of DAT-SPECT shows some clinical advantages in early diagnosis for Parkinson’s disease and differential from other non-degenerative parkinsonian disorders (i.e., essential tremor, dystonic tremor, drug-induced and in most cases of psychogenic parkinsonism), since it can accurately detect the presynaptic dopaminergic deficit. The test has been shown to have high sensitivity/specificity by multiple studies. DAT imaging may also have some prognostic value for disease progression. However, it has limited value in differentiating among degenerative causes of parkinsonism. Clinical assessment remains the most important aspect in evaluating these patients. DAT imaging has some limitations. In most studies, true test accuracy is unknown since the gold standard is clinical diagnosis by a movement disorders neurologist. Therefore, the sensitivity of the test cannot exceed that of the clinical diagnosis. In addition, false negative scans occur and highlight the need for clinical follow-up. DAT-SPECT is a sensitive modality to detect nigrostriatal degeneration. In spite of increasing data using this technique, however, more long-term clinical studies are required to determine how DAT-SPECT scan can guide decision-making.