<p>The aryl hydrocarbon receptor (AhR) is a key protein involved in numerous metabolic processes and signaling pathways across various cell types. Part of the basic helix-loop-helix (bHLH) transcription factor family, AhR contains a central PER-ARNT-SIM (PAS) domain crucial for binding ligands. When AhR binds to xenobiotic (toxic) substances, it becomes activated and influences a range of biological functions, such as cell proliferation, apoptosis, adhesion, differentiation, and the regulation of other transcription factors. However, the binding of certain ligands can also trigger harmful effects, contributing to disease development. Given that AhR serves as a link between the body and the external environment, understanding its response to environmental toxins, xenobiotics, and carcinogens is vital. Yet, studying AhR’s role in toxicology, physiology, and disease is challenging due to limited structural data. To overcome this, computational molecular modeling techniques like molecular docking, molecular dynamics (MD) simulations, and homology modeling have become crucial tools in AhR research. These methods provide valuable insights into how AhR is activated, its modulatory effects, and help complement experimental studies. This review highlights the use of in silico approaches to better understand AhR activation, its role in biological activities, disease progression, and potential therapeutic applications. </p>