Acute kidney injury is common in intensive care patients and continuous renal replacement therapy is the preferred treatment for this in most centres. Although these techniques have been adopted internationally, there remains significant variation with regard to their clinical application. This is particularly pertinent when one considers that the fundamental questions regarding any treatment, such as initiation, dose and length of treatment, remain a source of debate and have not as yet all been fully answered. In this narrative review we consider the timing of renal replacement therapy, highlighting the relative paucity of high quality data regarding this fundamental question. We examine the role of the usual biochemical criteria as well as conventional clinical indications for commencing renal replacement therapy together with the application of recent classification systems, namely RIFLE and AKIN. We discuss the potential role of biomarkers for acute kidney injury as predictors for the need for renal support and discuss commencing therapy for indications other than acute kidney injury.