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Stroke is a leading cause of death and disability worldwide. However, our understanding of its underlying biology and the number of available treatment options remain limited. Mendelian randomization (MR) offers a powerful approach to identify novel biological pathways and therapeutic targets for this disease. Around ~100 MR studies have been conducted so far to explore, confirm, and quantify causal relationships between several exposures and risk of stroke. In this review, we summarize the current evidence arising from these studies, including those investigating ischemic stroke, hemorrhagic stroke, or both. We highlight the different types of exposures that are currently under study, ranging from well-known cardiovascular risk factors to less established inflammation-related mechanisms. Finally, we provide an overview of future avenues of research and novel approaches, including drug target validation MR, which is poised to have a substantial impact on drug development and drug repurposing.