Diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). Conversely, chronic renal failure (CRF) is also associated with diverse alterations in carbohydrate and insulin metabolism. CRF-induced metabolic disorders should be borne in mind when treating diabetic patients, to ensure the introduction of adequate therapy adjustments that are in line with the onset of renal function decline. Moreover, several specific therapies employed in CRF may also influence pharmacological therapy of DM in uraemic patients. Adequate glycaemic control has also been associated with a reduction in the onset and progression of diabetic nephropathy as well as in the morbidity and mortality in uraemic diabetic patients during dialysis. Intensive insulin therapy can notably improve glycemic control and it should be considered part of the management of insulin-treated CRF diabetic patients. Insulin analogues have been recently evaluated in CRF diabetic patients, with encouraging results. In this study, we review the more relevant aspects related to insulin therapy in diabetic patients with different degrees of renal failure and in patients with ESRD, both in conservative therapy and dialysis.