This chapter provides a brief review of the experimental and computational methods for drug discovery. The chapter begins with the description of methods for three-dimensional structure determination, which is of high importance for understanding recognition mechanisms in a ligand–receptor system. Methods for searching quantitative structure–activity relationships are also discussed. However, methods for evaluating and modeling ADMET properties are not reviewed, as this topic is out of scope. Methods used in drug discovery for the estimation of binding affinity and activity en masse are described.