Diabetic retinopathy (DR) may lead to vision-threatening complications in people living with diabetes mellitus. Decades of research have contributed to our understanding of the pathogenesis of diabetic retinopathy from non-proliferative to proliferative (PDR) stages, the occurrence of diabetic macular oedema (DMO) and response to various treatment options. Multimodal imaging has paved the way to predict the impact of peripheral lesions and optical coherence tomography-angiography is starting to provide new knowledge on diabetic macular ischaemia. Moreover, the availability of intravitreal anti-vascular endothelial growth factors has changed the treatment paradigm of DMO and PDR. Areas of research have explored mechanisms of breakdown of the blood-retinal barrier, damage to pericytes, the extent of capillary non-perfusion, leakage and progression to neovascularisation. However, knowledge gaps remain. From this perspective, we highlight the challenges and future directions of research in this field.