Covalent modification of G protein-coupled receptors (GPCRs) by employing specific molecular probes has for decades provided a successful strategy to facilitate the elucidation of the structure and function of this pharmacologically important class of membrane proteins. The ligands typically comprise a pharmacophore that generates affinity for a given GPCR and contain a reactive functionality that may form a covalent bond with a suitably positioned amino acid residue. Covalent ligands have been successfully applied to circumvent poor affinity of compounds when stable labeling of receptor populations was required, and they have been used in the isolation, purification, and pharmacological characterization of specific subtypes of GPCRs. Recently, structural studies have demonstrated that covalent molecular probes are effective at stabilizing GPCRs to obtain X-ray crystal structures, thus providing valuable insights for the development of novel therapeutics. Herein, we review covalently binding molecular probes for class A GPCRs with a focus on ligands comprising cross-linking groups that do not require photoactivation and further highlight their significant and diverse applications.