Meningiomas, the most prevalent primary intracranial tumor, arise from the arachnoid cap cells in the meninges, the membranes that surround the brain and the spinal cord. The field has long sought effective predictors of meningioma recurrence and malignant transformation, as well as therapeutic targets to guide intensified treatment such as early radiation or systemic therapy. Novel and more targeted approaches are currently being tested in numerous clinical trials for patients who have progressed after surgery and/or radiation. In this review, the authors discuss relevant molecular drivers that have therapeutic implications and examine recent clinical trial data evaluating targeted therapies and immunotherapies.