As human genetics and genomics have progressed, culminating in the completion of the rough draft of the human genome in February 2001, new tools and technologies have been developed to identify and quantify global gene expression changes occurring in the cell. These new technologies are allowing researchers to gain an increased understanding of the function and regulation of genes at the systems level, and are transforming virtually all areas of biological research. In the field of toxicology, a new subdiscipline termed toxicogenomics has emerged which promises to identify and characterize the molecular mechanisms that lead to toxicity. Gene expression profiling, through the use of microarray technology, is rapidly becoming a standard analysis in toxicology studies, and has the potential to play a pivotal role in all stages of drug safety evaluation. This review focuses on recent studies in toxicogenomics, and discusses the promises and future challenges in this field.