Increasing our knowledge on the molecular and cellular mechanisms of acute renal tubular pathologies will lead to potential novel therapeutic strategies either to prevent the initiation of renal failure or to promote the renal regeneration after injury. Currently many genomic- and proteomic-based techniques are available to identify genes, proteins or protein modifications in relation to renal toxicity. Although we are able to identify many genes and proteins at once, the actual role of the genes and proteins with respect to cellular toxicity needs to be defined in order to better understand the molecular basis of renal cell injury and repair. This review will focus on the relationship between changes in gene and protein expression, cellular perturbations, signal transduction, and mechanisms of toxicity. A focus is on the role of stress response proteins in repair of injured renal cells.