The mechanism for the final step of Aromatase (AR) and the mode of action of some steroidal and non-steroidal inhibitors are studied with a molecular modelling approach involving consideration of the positioning of the P-450 heme with respect to the substrate backbone — the “substrate-heme complex”. This study suggests that Aminoglutethimide (AG) type compounds mimic the steroid C(17) carbonyl and not the C(3) carbonyl group as previously suggested by other workers. It also shows that inhibitors based on pyridine ligands such as 3-(4′-pyridyl)-3-ethyl piperidine-2,6-dione (PYG) utilise the steroid C(3) carbonyl binding region, thereby agreeing with other workers. Consideration of the orientation of the R and S enantiomers of PYG shows a reversal of results previously reported. By using inhibitors bound to the “substrate-heme complex”, and data from previous studies of derivatives of androstenedione, reasons for the differences in activity of enantiomers of AG, PYG, N-octyl-3-(4′-pyridyl)-3-ethyl piperidine-2,6-dione and 10-thiiranylestr-4-ene-3,17-dione, as well as other potent and less potent inhibitors, are suggested. The study also considers the three mechanisms of aromatisation, as proposed by Wright and Akhtar, from a geometric point of view and concludes that only a ferroxy radical is involved in all three steps of aromatisation, and not the mixture of both ferroxy and peroxy as previously postulated. An alternative theoretical mechanism, which circumvents the production of the CHO radical for the final step of aromatisation, is suggested.