G-protein-coupled receptors (GPCRs) are a large superfamily of plasma membrane proteins that play central roles in transducing endocrine, neural and -sensory signals. In humans, more than 30 disorders are associated with mutations in GPCRs and these proteins are common drug development targets, with 30-50% of drugs targeting them. GPCR mutants are frequently misfolded, recognized as defective by the cellular quality control system, retained in the endoplasmic reticulum and do not traffic to the plasma membrane. The use of small molecules chaperones (pharmacological chaperones or "pharmacoperones") to rescue misfolded GPCRs has provided a new approach for treatment of human diseases caused by misfolding and misrouting. This chapter provides an overview of the molecular basis of this approach using the human gonadotropin-releasing hormone receptor (hGnRHR) as model for treatment of conformational diseases provoked by -misfolded GPCRs.