Proteins are involved in virtually every process within biological systems, and the function that a protein assumes depends on its structure. Determining the structure of a protein is of fundamental importance to understanding protein interactions, the role of proteins in diseases and disorders, drug design and more. Cryo-electron microscopy (cryo-EM) was developed as a cutting-edge alternative to X-ray crystallography, and alleviates the need for crystallization. With recent advances in electron detection and image processing, the resolution by cryo-EM is now beginning to rival X-ray crystallography. Our goal is to employ cryo-EM to determine high resolution structures of important membrane protein complexes involved in cellular signaling, including cellular receptors and ion channels. We also combine structural approaches with functional studies to reveal the structure-function relationships of these membrane proteins.