Cerebral small vessel disease (cSVD) is a heterogeneous group of age-related pathologies affecting multiple brain regions. It encompasses a range of lesions detected on neuroimaging, from white matter hyperintensities to microbleeds, and can lead to severe disability and cognitive impairment. cSVD accounts for about 25% of ischemic strokes and most spontaneous intracerebral hemorrhages, and is a significant contributor to dementia. Despite its high prevalence and potential therapeutic window, there are currently no mechanism-based treatments. This review highlights recent advances in understanding cSVD, including the continuum between monogenic and multifactorial forms involving genes like NOTCH3, HTRA1, and COL4A1/A2. It discusses the relationships between risk factors, structural and functional vessel changes, and disease manifestations, emphasizing the need for further research in endothelial dysfunction and other perivascular cells. The review also explores vascular pathology, including arteriolosclerosis, and the impact on blood flow, neurovascular coupling, and fluid regulation in the brain. Finally, it addresses the challenges in understanding the pathogenesis of cSVD and the potential for developing effective treatments.Cerebral small vessel disease (cSVD) is a heterogeneous group of age-related pathologies affecting multiple brain regions. It encompasses a range of lesions detected on neuroimaging, from white matter hyperintensities to microbleeds, and can lead to severe disability and cognitive impairment. cSVD accounts for about 25% of ischemic strokes and most spontaneous intracerebral hemorrhages, and is a significant contributor to dementia. Despite its high prevalence and potential therapeutic window, there are currently no mechanism-based treatments. This review highlights recent advances in understanding cSVD, including the continuum between monogenic and multifactorial forms involving genes like NOTCH3, HTRA1, and COL4A1/A2. It discusses the relationships between risk factors, structural and functional vessel changes, and disease manifestations, emphasizing the need for further research in endothelial dysfunction and other perivascular cells. The review also explores vascular pathology, including arteriolosclerosis, and the impact on blood flow, neurovascular coupling, and fluid regulation in the brain. Finally, it addresses the challenges in understanding the pathogenesis of cSVD and the potential for developing effective treatments.