Simple SummaryWhole-brain radiation therapy (WBRT) has been a mainstay in the treatment of multiple cerebral metastases for many decades. However, evidence of its negative effects on cognitive functions and quality of life has rendered conventional WBRT unwanted and led to widespread use of local stereotactic therapies instead. However, newer WBRT methods have been proven to be efficient and safe and have become readily available in past years. No clinical trials have compared the oncological and functional outcomes of multiple radiosurgeries with these newer methods. The available data suggest that modern WBRT techniques can play a significant role in the treatment of multiple brain metastases and warrant further prospective research.Abstract(1) Background: In recent decades, the use of whole-brain radiation therapy (WBRT) in the treatment of brain metastases has significantly decreased, with clinicians fearing adverse neurocognitive events and data showing limited efficacy regarding local tumor control and overall survival. The present study thus aimed to reassess the role that WBRT holds in the treatment of brain metastases. (2) Methods: This review summarizes the available evidence from 1990 until today supporting the use of WBRT, as well as new developments in WBRT and their clinical implications. (3) Results: While one to four brain metastases should be exclusively treated with radiosurgery, WBRT does remain an option for patients with multiple metastases. In particular, hippocampus-avoidance WBRT, WBRT with dose escalation to the metastases, and their combination have shown promising results and offer valid alternatives to local stereotactic radiotherapy. Ongoing and published prospective trials on the efficacy and toxicity of these new methods are presented. (4) Conclusions: Unlike conventional WBRT, which has limited indications, modern WBRT techniques continue to have a significant role to play in the treatment of multiple brain metastases. In which situations radiosurgery or WBRT should be the first option should be investigated in further studies. Until then, the therapeutic decision must be made individually depending on the oncological context.