Cytochrome P450 (CYP) enzymes play an important role in the phase I metabolism of many xenobiotics. Most drug-drug interactions (DDIs) associated with CYP are caused by either CYP inhibition or induction. The early detection of potential DDIs is highly desirable in the pharmaceutical industry because DDIs can cause serious adverse events, which can lead to poor patient health and drug development failures. Recently, many computational studies predicting CYP inhibition and induction have been reported. The current computational modeling approaches for CYP metabolism are classified as ligand- and structure-based; various techniques, such as quantitative structure-activity relationships, machine learning, docking, and molecular dynamic simulation, are involved in both the approaches. Recently, combining these two approaches have resulted in improvements in the prediction accuracy of DDIs. In this review, we present important, recent developments in the computational prediction of the inhibition of four clinically crucial CYP isoforms (CYP1A2, 2C9, 2D6, and 3A4) and three nuclear receptors (aryl hydrocarbon receptor, constitutive androstane receptor, and pregnane X receptor) involved in the induction of CYP1A2, 2B6, and 3A4, respectively.