Serotonin neurons are highly plastic; their development, maturation and regeneration is controlled by a complex gene regulatory network in constant interaction with the environment. An overview article recently published in WIREs Developmental Biology offers an updated view of these fundamental developmental mechanisms, pointing to the many ways by which developmental dysfunction of serotonin systems might occur at different periods in life. This opens new possibilities for therapeutic intervention, which can range from prevention of risk to stem cell therapies.