Humans usually attribute themselves the prerogative of being the pinnacle of evolution. They have large brains with many billion neurons and glial cells (Lent et al., 2012), trillions of synapses and besides all, a plastic hardware that may change either subtly or strongly in response to the external or internal environment (Tovar-Moll et al., 2014). With this hypercomplex apparatus, they are capable of very sophisticated inward computations and outward behaviors that include self-recognition, metacognition, different forms of language expression and reception, prediction of future events, planning and performing long streams of motor acts, subtle emotional feelings, and many other exceedingly complex properties.The main challenge for research is: how do we explain this gigantic achievement of evolution? Is it a direct consequence of having acquired a brain larger than our primate ancestors, with huge numbers of computational units? Would it be determined by a particular way these units came to relate to each other, building up logic circuits of powerful capacities? What along development has "made the difference" for the construction of such a complex brain machine? How much of this complexity is innate, how much is sculpted by influence of the external world, by social interaction with our human fellows, and by the history of our own mental trajectory along life?This special issue of Frontiers addresses some of these intriguing issues. It is comprised of ten reviews by experts in the field.A reductionist approach is taken by Seth Dobson from Dartmouth College, and Lauren Brent from Duke University, USA. They examine how genomic features of individuals link up to behavioral patterns, in health and disease. Their hypothesis is that polymorphisms of the serotonin transporter gene, typical of primates including humans, offer allelic diversity that make some of us more prone to face adverse social situations (those expressing low levels of the transporter proteins), while others deal better with nonconflictive daily situations (those with high levels). Having two different alleles, therefore, provides long-term benefits to the species to face diverse competition levels within the social group.Branka Hrvoj-Mihic and her collaborators from the University of California at San Diego, USA, comment about an old suggestion by Greenough et al. (1987) on the two basic mechanisms of plasticity: experience-expectant plasticity, by which the brain is provided by development with exuberant hardware (connections, dendrites, synapses), sculpted postnatally to achieve the best configuration for survival; and experience-dependent plasticity, associated to the critical periods in development, by which our late-maturing brain allows change and modulation oriented by environmental input. They argue that the brain faces two opposing needs along life: one is to maintain its circuitry functionally stable, the other is to provide it with enough flexibility (=plasticity) to respond appropriately to the environment.