In summary, fluoxetine is a highly selective serotonin uptake inhibitor in vitro and in vivo. The conformation of fluoxetine, which resembles that of sertraline and other serotonin uptake inhibitors, appears to be a key feature that enables its high affinity and selective interaction with the serotonin transporter. The para-trifluoromethyl substituent, however, is also a pivotal structural element. The molecular pharmacology of fluoxetine has been well-defined, and its in vivo pharmacological effects appear to be mediated almost exclusively by serotonin uptake inhibition. Its selectivity for the serotonin transporter, lack of affinity for neurotransmitter receptors, and retention of selectivity following metabolism to norfluoxetine make fluoxetine a useful tool to explore pharmacologically induced increases in serotonin neurotransmission. Fluoxetine has found a variety of therapeutic application. Its use in treating depression has been most extensively studied, but controlled clinical studies also suggest the drug may have a role in treating obesity and bulimia. Moreover, a variety of other psychiatric disorders may be treatable with this drug. Regardless of the outcome of these clinical trials, it is apparent that fluoxetine has found a useful niche in therapy, and can be used as a probe to determine the role of serotonin in modulating human pathophysiologies.