Despite the massive investments made by pharmaceutical companies on drug research and development, the number of new drug approvals has remained stagnant in the past decades. It is well known that developing safe and effective new drugs is a long, difficult, and expensive process. While the cost of developing new drugs is increasing rapidly, withdrawals of drugs from the marketplace due to adverse drug reactions (ADR) and/or toxicity is increasing concurrently. The recent advent of high-throughput in silico (computer softwares) and in vitro (cell cultures) screenings have somewhat alleviated some, but not all, of these challenges by providing an efficient and effective way for developing safer and better drugs. This emerging technology, known as toxicogenomics, has great potential to facilitate the development of methodologies that could predict the long-term toxic effects of compounds using relatively short-term bioassays. This review is aimed at discussing the potential applications and future challenges of toxicogenomics in drug discovery and drug development.