The discovery and launch of non-steroidal ligands for estrogen receptors (ERs) and for androgen receptors (ARs) demonstrated the potential of these ligands as therapeutic agents. Based on these successes, substantial attention in the past ten years has been focused on identifying non-steroidal ligands for all of the classic steroid receptors. Non-steroidal ligands are currently in the discovery phase or in early clinical development for glucocorticoid, mineralocorticoid and progesterone receptors, and therefore must still provide evidence of their beneficial features over their steroidal counterparts. Although many new compounds for ERs and ARs are also undergoing discovery phase investigation or (early) development, none have been launched in the past ten years. The complexity of steering functional selectivity remains an ongoing challenge in the development on non-steroidal ligands.