Some compounds can fail in the latter stages of drug development because of lack of efficacy and toxicity. To improve drug safety in the development process, new biomarkers are needed which can reduce the time-consuming process and cost of drug development. Traditional indicators of target organ toxicity used in preclinical drug safety studies consist of a battery of clinical pathology parameters in blood and urine coupled with histopathologic examination of altered tissues. Researching the translational safety biomarker is a process that investigates one characteristic of the biomarker, i.e. noninvasive, and translates between species. The safety biomarker should be validated and preclinically and clinically qualified. Several urinary/kidney biomarkers in the context of preclinical development and clinical trials are presented in this chapter. Application of safety biomarkers in different phases of drug development, in particular for kidney, liver, heart, vascular vessels, lung, central nervous system, and lipid/carbohydrate metabolism, are described.