This paper reviews practice in the area of intramuscular (IM) injection administration, an everyday activity for many nurses in clinical practice. The authors address administration of neuroleptic depot drugs within the adult mental health environment and examine the evidence base for this practice. A historical overview of injection practices and use of the dorsogluteal site is given, followed by more contemporary evidence on the benefits of using the ventrogluteal, deltoid and thigh sites. The authors point out that despite being a very commonplace nursing activity, there is a dearth of research-based guidelines for nurses in this area. A quantity of published papers and nursing texts on injection sites and techniques were assessed to evaluate their quality and relevance and their overall benefit to improving clinical practice. Much of the literature available was in the form of opinion pieces without a sound research/evidence base. There appears, however, to be enough consensual evidence to form an evidence-based clinical guideline for the administration of IM injections. The review of the available evidence, albeit at times contradictory, is presented along with a discussion of the implications for nurses.