As we enter the era of personalized medicine, tests that can inform on molecular mechanisms of cancer, and on breast cancer in particular, are in high demand. We currently use DNA- or RNA-based tests of gene expression and/or immunohistochemistry to better characterize a given breast cancer and aid the clinician in selecting the best treatment options. In breast cancer, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) are established biomarkers. There are several ways to obtain information on these biomarkers, including invasive testing (biopsy), which can be challenging depending on the location. However, not all tumors that express targets identified by tissue assay will respond to directed therapy. Nuclear imaging tests can be useful in these situations. They can be used as a noninvasive method for detecting tumor, obtaining information about the biology of the tumor, and predicting which tumors will respond to targeted therapies. Here, we will review how radiolabeled glucose and estrogen analogs can be used in breast cancer patients. We focus this review on the application of positron emission tomography (PET) imaging to ER-positive metastatic breast cancer as an example of how imaging can guide breast cancer treatment.