Development of “biased ligands” preferentially activating specific signaling pathways by stabilizing subsets of receptor conformations that invoke distinct G protein-dependent or -independent signaling are underway. Development of novel analgesics acting via CB1, μ-, δ- and κ-opioid receptors is focused on identification of G protein-selective compounds that are devoid of β-arrestin 2 recruitment because evidence suggests that this may reduce adverse effects. Results of these efforts appear promising in vitro, but in vivo confirmation of biased agonism is relatively rare. This symposium will survey biased agonism across pharmacological classes, focusing on behavioral effects which may differentiate them from traditional unbiased agonists.