This report provides a review on quantitative structure–activity relationship (QSAR) modeling, approaches, and its various applications in biological systems. Quantum chemical methods and modeling techniques help in correlating a specific activity for a set of compounds with their structure-derived descriptors by means of a mathematical model. Such models have been widely applied in many fields including chemistry, biology, and environmental sciences. Computational tools or in silico method are cost-effective approaches, which ultimately help in reducing the in vivo experiments on animals also. This study is mainly focused on the method for QSAR modeling as well as the method for systematic comparison of the theoretical molecular descriptors with experimental descriptors.