The role played by environmental influences in the development of the nervous system has been subject to intense study for the last three decades. Many laboratories are currently engaged in characterizing the exact contributions of activity-dependent or -independent processes to the development of the mammalian neocortex. Here we introduce a special issue devoted to the topic and briefly review recent progress in this exciting field. At the systems level, many investigators are now distinguishing between an "establishment" phase of cortical connections, where activity-dependent and independent mechanisms could operate, and a later "maintenance" phase, which appears to be controlled by neuronal activity. A particularly interesting recent example of the role of top-down vs. bottom-up influences in the development of cortical connections is the emergence of orientation selectivity in visual cortex: we propose a synthetic view highlighting the role of the thalamo-cortical reciprocal projection in this process. Finally, at the cellular level, NMDA receptors, neurotrophins and many other molecules contribute to activity-dependent rearrangement of cortical connections during appropriate critical periods of development.