Acute kidney injury (AKI) is a very relevant and increasing health and socioeconomic problem worldwide. In critically ill patients, mortality to AKI may reach up to 50-80% of the cases. Even mild, spontaneously reversible episodes of AKI have a significant impact on medium and long term morbidity and mortality. Drug nephrotoxicity is among the most important causes of AKI, with 25% of the 100 most used drugs in intensive care units being nephrotoxic. AKI has been traditionally diagnosed when extensive renal damage gave way to signs derived from renal dysfunction, such as the elevation of plasma creatinine concentration, according to well established methods of stratification, including the AKIN and RIFLE criteria. In the last decade, further advance was provided by the identification of earlier markers of kidney injury, including KIM-1 and NGAL. Yet, more sensitive and specific markers, or combinations of markers, are needed to improve AKI diagnosis. However, new facets of AKI diagnosis emerge for a more personalized and preventive handling of this disease. In the last years, our group has been working on two new diagnostic concepts, namely: i) pre-emptive detection of drug-induced predisposition to AKI, as differentiated from early diagnosis; and ii) aetiological (drug-specific) diagnosis of AKI, potentially applicable to polymedicated patients.