Diuretics remain a common medication in Paediatric practice and possibly one of the most important drugs in Nephrology practice. Understanding their mechanism, appropriate rationale for use and prompt identification of side-effects allows for high efficacy and safety in their use. On the back-ground of challenges in our center with regards to the use of frusemide, this review is specifically focused on addressing factors that may affect frusemide efficacy, possible cause of resistance and drug interactions that may occur following its use.