G protein-coupled receptors (GPCRs) are vital cellular signaling machinery that are dependent on the membrane environment in which they reside. For instance, cholesterol has been reported to be critical for different aspects of GPCR function, such as ligand binding, G-protein coupling, receptor stability, organization, and dynamics. Multiscale simulation approaches have helped complement experimental approaches in probing the interplay of GPCRs with their surrounding lipids. The large complexity and diversity of membrane lipids, coupled with their stochastic interactions spanning multiple timescales, necessitate the use of such a multi-pronged approach. In this chapter, we discuss the considerations needed to set up atomistic and coarse-grain simulations, and the related analysis methods to extract robust and meaningful values of receptor-lipid interactions. We discuss crucial aspects of the simulation setup, including selecting appropriate lipid compositions. We then explore both qualitative and quantitative approaches for analyzing GPCR-lipid interactions, ranging from occupancy values and enrichment indices to free energy calculations and residence time analyses. In addition, we highlight approaches to identify synergistic co-binding, as well as competitive binding of lipids to GPCRs, a phenomenon that is often neglected in model membrane studies. This comprehensive overview will help researchers to perform robust and informative simulations to elucidate the intricate interplay between GPCRs and their surrounding lipid bilayer