The cell surface, or surfaceome, plays a critical role in cell communication, adhesion, and signaling. This volume provides a comprehensive collection of protocols designed to explore the dynamic nature of the surfaceome. Encompassing both established and emerging techniques, this collection equips researchers with methods for isolating and characterizing surface proteins, analyzing protein–protein interactions, and investigating posttranslational modifications. It also includes protocols for advanced approaches, such as single-channel recordings and mass spectrometry–based analyses. Detailed instructions and troubleshooting tips empower researchers of all levels of experience to investigate the intricacies of the surfaceome. This collection serves as a resource for researchers in cell biology, biochemistry, and medicine aiming to understand the complexities of biological membranes and surfaceomes in health and disease.