Monoamines are phylogenetically ancient molecules that predate the evolution of the nervous system, and were likely co-opted to function as  neurotransmitters. Several monoamines retain ‘pre-nervous’ trophic-factor actions influencing development and growth, while exerting pleiotropic neurotransmitter effects on diverse brain functions and behaviour. Amongst them, specific monoamines are speculated to exert antioxidant-like actions, however their direct influence on the energy producing organelle, mitochondria and on a neuron’s cellular stress buffering capacity remain poorly understood. Mitochondria have recently emerged as important targets to consider both from the perspective of pathogenesis and treatment of psychiatric disorders. Mitochondria contribute to the buffering of stress-associated allostatic load, and mitochondrial dysfunction can hamper stress-adaptation and enhance risk for psychopathology. Mitochondrial function is essential to fulfil substantial neuronal metabolic demands, maintain excitability and facilitate synaptic transmission. Mitochondrial biogenesis is an adaptive mechanism that responds to cellular energetic demands and oxidative insults, and can promote neuronal viability. In my talk I will discuss results that link serotonin and norepinephrine to mitochondrial biogenesis in rodent cortical  and hippocampal neurons respectively, and enhanced mitochondrial function, respiratory capacity and ATP generation. These intriguing effects arise via recruitment of master modulators of mitochondrial biogenesis, the sirtuin SIRT1 and the transcriptional coactivator PGC-1α, that are strongly implicated in metabolic control and longevity. This link between monoamines, bioenergetics and neuronal survival provides a new framework for how monoaminergic neurotransmission impacts cellular stress responses. Our study motivates further investigation to address the contribution of mitochondrial modulation to the effects of monoamines on mood regulation, neuroplasticity and senescence.