The optimum parameters for single-shot gradient-recalled (GR) EPI-based fMRI studies of the limbic region are systematically established at 3 T via their ability to mitigate intravoxel dephasing—measured via SNR and T2* in the amygdalae—and their implications for temporal resolution (or brain coverage). Conventional imaging parameters (64 × 64 matrix size and 4–6 mm thick slices) are confirmed to be inadequate for functional studies at 3 T. Measurements of main magnetic field variations across the amygdalae suggest that such variations are equal in the craniocaudal and anterior–posterior directions, and slightly lower in the mediolateral direction, with this and other considerations leading us to conclude an oblique axial orientation to be most suitable. In-plane resolution of approximately 1.7 mm was sufficient to recover signal in the area of the amygdalae. SNR was found to peak at a slice thickness of between 2.0 and 2.5 mm, dependent on the subject. T2* time in the amygdalae was measured with a standard EPI protocol to be 22 ± 3 ms. Using the optimized (high resolution) EPI protocol proposed here, the measured T2* time increased to 48 ± 2 ms (compared with 43 ± 3 ms for a reference FLASH scan), only slightly lower than the cortex (49 ± 2 ms measured with optimized EPI and 52 ± 2 ms with FLASH). The FLASH measurement of 43 ms is taken to be a suitable effective echo time (TE_eff) to achieve maximum BOLD sensitivity in the amygdalae. Time series data acquired with these parameters showed a 60% increase in SNR in the amygdala over that obtained with a standard low-resolution protocol and suggest sufficient SNR and BOLD sensitivity to make functional studies feasible. Arteries, but no substantial draining veins, were found in high-resolution BOLD venograms of the region. Our results indicate that EPI protocols need to be carefully optimized for structures of interest if reliable results from single subjects are to be established in this brain region.