Drugs are launched to market after the lengthy process of development. Despite careful preclinical assessment, there is still a significant risk that a drug candidate may elicit adverse effects or display a low level of efficacy during clinical trials. If a drug candidate fails in the latter stages of the clinical process, the overall loss, both in terms of time and money, is enormous. A major concern for the pharmaceutical companies is to improve the drug development process to make it faster and more cost-effective by adoption of new technologies. Biomarkers are emerging as a key tool in identifying potential drug failures at an early stage or in helping to make go/no-go decisions, which should significantly accelerate drug development. Omics technologies play an important role in biomarker discovery as well as in other stages of the drug discovery and development (e.g. target discovery, mechanism of action or predicting toxicity). In particular, recent progress in mass spectrometry techniques such as selected reaction monitoring (SRM) and novel high-resolution features have helped facilitate the realization of the inherent power of proteomics and metabolomics in biomarker discovery, validation and qualification. In this manuscript, we review the current state of proteomics and metabolomics in conjunction with recent technical advances in mass spectrometry with some examples of applications in biomarker research. In addition, we discuss the possible impact of biomarker research with these technologies in drug discovery and development.