The methodologies of computational drug discovery and drug repositioning (DR) based on biomolecular profile information are reviewed systematically. For big data drug discovery and DR, 1) methods of comparing gene expression profiles of the diseased state and drug-administered state to predict the effect and toxicity of the drug, 2) DR methods based on the disease network, and 3) prediction of drug effect based on the biological network analysis are described. For methods of AI-based drug discovery, virtual screening using AI and AI-based drug target exploration are reviewed.