Systematic inoculation experiments were carried out to study the influence of various inclusions on the nucleation of the α-Al phase in Al-Si-Fe alloys at different cooling rates. The results showed that in dilute alloys, containing less than 1.5 pct Si+Fe, almost all the inclusion types have high percentages of occurrence within the α-Al phase, indicating that nucleation can be promoted on the surface of such inclusions. In a hypoeutectic Al-Si alloy containing 6.3 pct Si, the inclusion particles of MgO, TiB2, TiC, α-Al2O3, and SiC become mostly inactive nucleants and are pushed to the interdendritic regions because of the dominating poisoning effect of Si. The current results were used successfully to explain the efficiency differences between the commercial grain refiners in the hypoeutectic Al-Si alloys. Silicon is observed to preferentially segregate to the liquid-Al/inclusion interfaces so as to lower the free energy of such interfaces. A theoretical analysis of the poisoning effect of Si showed that Si segregation to the liquid/nucleant interface alters the interfacial energy balance so that the catalytic efficiency of the nucleant particles is dramatically reduced. Careful analysis showed that the poisoning effect of Si in the hypoeutectic alloy is overcome when the nucleant particles have active surface characteristics, as represented by the high catalytic potencies of γ-Al2O3, CaO, and Al4C3 particles in nucleating the α-Al phase of the hypoeutectic Al-Si alloy. Although some inclusions have comparable or higher occurrence levels than TiB2 in the α-Al phase, they cannot be used as efficient nucleants because of either their poor wettability with liquid aluminum or their chemical reactivity, which can change the alloy chemistry.