Triple Whammy (TW) is a dangerous drug interaction (DI) that can occur when combining angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), with diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). One of the most serious consequences of TW is contributing to pre-renal acute kidney injury (pr-AKI). Due to the fact that the term TW, in context of DI affecting kidneys function is not very widespread, the aim of this article was to gather information on this interaction. Previous knowledge on the mechanism of TW and increasing patient awareness of this interaction is described. In addition, the specific nature of the acute kidney injury (AKI) caused by triple whammy (AKITW) is presented. On the basis of the current state of knowledge, recommendations how to manage the TW DI are also demonstrated.