Secondary hyperparathyroidism (sHPT) is one of the most common and serious complications of chronic kidney disease (CKD) and maintenance hemodialysis (MHD). In sHPT, the biology of parathyroid cells changes significantly toward diffuse and nodular hyperplasia. Diagnosis and treatment of sHPT are based on intact parathyroid hormone (i-PTH) serum levels and on the parameters of mineral metabolism. The morphological diagnosis of sHPT relies on 2 complementary imaging techniques: high-resolution ultrasonography with color Doppler imaging (US/CD) and 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy. The main objective of this review is to stimulate nephrologists to use US/CD of the parathyroid glands during the progression of CKD in order to aid clinical, pharmacological and surgical strategies. The primary role of US/CD in sHPT should be to integrate the clinical diagnosis by defining the number and volume of hyperplastic glands, although the international guidelines do not state when and why to perform US/CD. This review also evaluates the role of US/CD in clinical follow-up and assessment of therapeutic response of sHPT, and it highlights how US/CD can evaluate the effect of therapy with phosphate binders, vitamin D or its analogues and calcimimetics, which are changing the natural history of sHPT and the frequency of parathyroidectomy. Evaluation of the morphological and vascular changes of hyperplastic parathyroids is useful to guide percutaneous ethanol injection therapy and to support clinical, pharmacological and surgical strategies. Epidemiological studies are needed to establish how US/CD could change the management of sHPT and why it should be repeated in patients with high levels of serum i-PTH.