The burden of microvascular disease in patients with type 2 diabetes mellitus continues to escalate worldwide. Current standards of care reduce but do not eliminate the risk of diabetic retinopathy, nephropathy or neuropathy in these patients. Correction of atherogenic dyslipidemia, which is characterized by elevated triglyceride levels and low levels of HDL cholesterol, might provide additional benefit. Whereas promising data have been published with respect to fibrate therapy for maculopathy, fenofibrate for diabetic retinopathy, and statin or fibrate therapy for diabetic nephropathy, further studies are warranted to define optimal management strategies for reducing the residual microvascular risk. Such strategies are especially relevant in cases of diabetic peripheral neuropathy, where even optimal care fails to affect disease progression. Identification of those factors that are most relevant to residual diabetes-related microvascular risk is a priority of an ongoing multinational epidemiological study. In this Review, we highlight an urgent need to address the issue of microvascular residual risk in patients with or at risk of type 2 diabetes mellitus.