Histopathology is the gold standard when defining toxicological effects, but it is invasive, time consuming and expensive. Using biomarkers linked to distinct, defined cell types and tissues may provide a direct link to histopathology without its drawbacks and it also provides increased sensitivity and specificity. Furthermore, as histological testing is often impractical in human subjects, using biomarkers with a known histological distribution may fill the need of localising toxic injury to distinct organs or tissues. This paper discusses how, by using biomarkers with a known cellular origin (histologically defined biomarkers), toxic effects may be found earlier and at lower doses of compound, leading to potential savings in drug development.