Preoperative imaging has proved its use successful in the localization of solitary parathyroid adenomas in patients with suspected primary hyperparathyroidism. However, due to multiglandular disease at presentation patients with renal hyperparathyroidism need to be analyzed separately, making the usefulness of imaging techniques controversial. Recently, improved methods of functional imaging like parathyroid scan with 99mTc-sestamibi or positron emission tomography, especially when combined with computed tomography, can provide additional quantitative and qualitative information that has yet to be assessed. Nuclear medicine procedures could prove useful not only in preoperative diagnosis, but also in the selection of medical or surgical therapeutic alternatives in secondary hyperparathyroidism patients. There is evidence that 99mTc-sestamibi uptake in parathyroid hyperplasia or adenoma is related to biochemical markers of parathyroid function. We are only beginning to identify the factors involved in radiotracer uptake by parathyroid cells and how it can be modulated to obtain more accurate results. This review analyzes the current use of non-invasive imaging modalities in patients with secondary hyperparathyroidism, taking into account the latest trends in the field combining anatomic and functional modalities and the relevant factors linked to radiotracer uptake in abnormal hyperfunctioning parathyroid glands.