Diffusion-weighted imaging (DWI) has revolutionised stroke imaging since its introduction in the mid-1980s, and it has also become a pillar of current neuroimaging. Diffusion abnormalities represent alterations in the random movement of water molecules in tissues, revealing their microarchitecture, and occur in many neurological conditions. DWI provides useful information, increasing the sensitivity of MRI as a diagnostic tool, narrowing the differential diagnosis, providing prognostic information, aiding in treatment planning and evaluating response to treatment. Recently, there have been several technical improvements inDWI, leading to reduced acquisition time and artefacts and enabling the development of diffusion tensor imaging (DTI) as a tool for assessing white matter.We aim to review the main clinical uses of DWI, focusing on the physiological mechanisms that lead to diffusion abnormalities. Common pitfalls will also be addressed. Teaching Points • DWI includes EPI, TSE, RESOLVE or EPI combined with reduced volume excitation. • DWI is the most sensitive sequence in stroke diagnosis and provides information about prognosis. • DWI helps in the detection of intramural haematomas (arterial dissection). • In diffusion imaging, ADC is inversely proportional to tumour cellularity. • DWI and DTI derived parameters can be used as biomarkers in different pathologies.