Recent applications of oxygen-sensitive microsensors have demonstrated steep oxygen gradients in developing seeds of various crops. Here, we present an overview on oxygen distribution, major determinants of the oxygen status in the developing seed and implications for seed physiology. The steady-state oxygen concentration in different seed tissues depends on developmental parameters, and is determined to a large extent by environmental factors. Photosynthetic activity of the seed significantly diminishes hypoxic constraints, and can even cause transient, local hyperoxia. Changes in oxygen availability cause rapid adjustments in mitochondrial respiration and global metabolism. We argue that nitric oxide (NO) is a key player in the oxygen balancing process in seeds, avoiding fermentation and anoxia in vivo. Molecular approaches aiming to increase oxygen availability within the seed are discussed.