Despite decades of research, the biochemical and neurophysiological causes of depression remain unknown. Furthermore, although selective serotonin reuptake inhibitors (SSRIs) block the reuptake of serotonin and alleviate depression in some patients, it is not clear how or why they work. Mathematical models of serotonin synthesis, release, and reuptake can shed light on the control mechanisms of the serotonin system and suggest hypotheses about the action of SSRIs. We will discuss two of the standard hypotheses and propose a new hypothesis. Parkinson?s disease has been traditionally thought of as a dopaminergic disease in which cells of the substantia nigra pars compacta (SNc) die. However, accumulating evidence implies an important role for the serotonergic system in Parkinson?s disease in general and in physiological responses to levodopa therapy, the first line of treatment. We use a mathematical model to investigate the consequences of levodopa therapy on the serotonergic system and on the pulsatile release of dopamine (DA) from dopaminergic and serotonergic terminals in the striatum. We will also ask, and propose an answer to, the question of what serotonin is doing in the striatum anyway?