It is well documented that psychostimulants may alter neuronal function and neurotransmission in the brain. Although the mechanism of psychostimulants is still unknown, it is known that these substances increase extracellular level of several neurotransmitters including dopamine (DA), serotonin, and norepinephrine by competing with monoamine transporters and can induce physical tolerance and dependence. In addition to this, recent findings also suggest that psychostimulants may damage brain neurons through mechanisms that are still under investigation. In the recent years, it has been demonstrated that almost all psychostimulants are able to affect a class of proteins, called neurotrophins, in the peripheral and central nervous system (CNS). Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), have relevant action on neurons involved in psychostimulant action, such as DA and serotonergic neurons, and can play dual roles: first, in neuronal survival and death, and, second, in activity-dependent plasticity. In this review, we will focalize on the effects of psychostimulants on this class of proteins, which may be implicated, at least in part, in the mechanism of the psychostimulant-induced neurotoxicity. Moreover, since altered neurotrophins may participate in the pathogenesis of psychiatric disorders and psychiatric disorders are common in drug users, one plausible hypothesis is that psychostimulants can cause psychosis through interfering with neurotrophins synthesis and utilization by CNS neurons.