Layer 4 neurons in primary sensory cortices receive direct sensory information from the external world. A general feature of these neurons is their selectivity to specific features of the sensory stimulation. Various theories try to explain the manner in which these neurons are driven by their incoming sensory information. In all of these theories neurons are regarded as simple elements summing small biased inputs to create tuned output through the axosomatic amplification mechanism. However, the possible role of active dendritic integration in further amplifying the sensory responses and sharpening the tuning curves of neurons is disregarded. Our findings show that dendrites of layer 4 spiny stellate neurons in the barrel cortex can generate local and global multi-branch N-methyl-D-aspartate (NMDA) spikes, which are the main regenerative events in these dendrites. In turn, these NMDA receptor (NMDAR) regenerative mechanisms can sum supralinearly the coactivated thalamocortical and corticocortical inputs. Using in vivo whole-cell recordings combined with an intracellular NMDAR blocker and membrane hyperpolarization, we show that dendritic NMDAR-dependent regenerative responses contribute substantially to the angular tuning of layer 4 neurons by preferentially amplifying the preferred angular directions over non-preferred angles. Taken together, these findings indicate that dendritic NMDAR regenerative amplification mechanisms contribute markedly to sensory responses and critically determine the tuning of cortical neurons.