Dopamine and serotonin receptors are central to brain function, yet are extremely challenging to study, especially in precise regions and narrow timescales. Our goal is to create new chemical tools to study dopamine and serotonin GPCRs in living mammals, without the need for genetic manipulation. Here, I discuss three of our current projects: 1) covalent probes for dopamine receptor D2 (DRD2) and serotonin receptors 5HT2A and 5HT2C; 2) photocaged, pharmacokinetically “matched” agonist/antagonist pairs for rapid control of signaling dynamics; and 3) synthesis and testing of a new photoswitchable pharmacophore to direct G-protein vs beta arrestin pathway bias.