Sibutramine is known to be effective in the treatment of obesity and is used worldwide by millions. It acts on the central nervous system by inhibiting the neuronal reuptake of serotonin and noradrenaline; there by also have possible psychologiocal effects. This article reviews animal studies as well as clinical trials done on the role of sibutramine in the treatment of obesity. Also, we hypothesise on possible psychological effects, focussing specific on the inhibition of the reuptake of serotonin in the brain, influencing depression. This article concludes with the hypotheses that patients who have a tendency for depression who uses sibutramine, might end up with ultimate low levels of serotonin in the brain. Also, we hypothesise on the possible potentiated effect of sibutramine and SSRI’s on the neuronal reuptake of serotonin.