This article briefly summarizes the occurrence of biphasic dose-response relationships associated with 5-hydroxytryptamine (5-HT) receptor systems, as well as 5-HT agonists and antagonists. Such biphasic responses have been reliably reported in multiple experimental settings that explored a broad range of responses, including aggressive behavior, cardiovascular functioning, muscle relaxation, and interactions with other receptor systems such as adrenergic interaction as well as with neurotransmitters such as NMDA.