Rate measurements for the reactions of a series of polyfluoro - and polychloro - pyridines with aniline and ammonia in 60/40 dioxan/water at 25ºC has shown that chlorine, when ortho and para to the position of attack, is activating with respect to fluorine, but at the position meta to the point of attack, chlorine and fluorine are virtually equivalent in their effect on reaction rate. The trifluoromethyl and nitrile groups were found to be activating relative to fluorine when ortho and para to the position of substitution and the nitrile group was thus found to be ortho/para directing. The ortho/para orienting effect of ring nitrogen was shown to be dominant in heterocyclic systems. It has been demonstrated for several different nucleophiles that nucleophilic attack in polyfluorinated heterocycles occurs so as to maximise the number of ortho and meta fluorines with fluorine being of little significance. Of the nucleophiles examined aniline and ammonia were found to be similar in their behaviour. Benzylamine however showed some propensity for substitution at positions ortho to ring nitrogen whilst N-methylaniline showed strong steric effects due to the N-methyl group, most notably when the heterocylic ring substituents were chlorine, trifluoromethyl and nitrile. Sodium was shown to have a 'salt effect' in the reactions of methoxide and phenoxide, and, a catalytic effect on the reactions of aniline affecting both the rate and position of substitution. The use of transition state, and molecular orbitals to explain the patterns of substitution is discussed. The trifluoromethylsilyl group was found to undergo nucleophilic attack at silicon and the series of mono, di and tri-fluoromethyl-pentafluorobenzenes were used to examine the concept of negative ion hyperconjugation.