Animal models are important experimental tools for investigating the molecular mechanisms, environmental and genetic susceptibilities underlying the development of thrombotic microangiopathies. Large mammal, small animal models, knockout, transgenic and conditional knockout mouse models are available to investigate haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura and vascular endothelial growth factor-associated thrombotic microangiopathy. These models have shown that it is possible to model the human conditions. However, differences in human and rodent physiology mean that caution is required when interpreting the findings. These models offer realistic prospects for identifying and testing novel therapeutic strategies in a range of thrombotic microangiopathies prior to human trials.