Venlafaxine (Effexor) is an effective antidepressant and has also been approved for the treatment of generalized anxiety disorder. Venlafaxine was initially characterized as an inhibitor of both serotonin (5HT) and norepinephrine (NE) uptake and was therefore termed a "dual uptake inhibitor." This chapter reviews data from both in vitro and in vivo studies regarding its effects on 5HT and NE neurotransmission. In addition, the effects of venlafaxine on other systems that may play a role in its therapeutic efficacy effects are described. The data indicate that venlafaxine is a relatively weak inhibitor of NE transport in vitro. In vivo studies indicate that venlafaxine selectively inhibits 5HT uptake at low therapeutic doses and inhibits both 5HT and NE uptake at higher therapeutic doses. This chapter concludes with a discussion of the effects of venlafaxine on various aspects of physiology.