According to Vasari, he not only finished the exterior from the second story upwards, but designed the whole of the central courtyard above the first story, "making it the finest thing of its sort in Europe." The interior, with the halls painted by Annibale Caracci, owed its disposition into chambers and galleries to his invention.

The cornice has always been reckoned among his indubitable successes, combining as it does salience and audacity with a grand heroic air of grace.

It has been criticised for disproportionate projection; and Michelangelo seems to have felt uneasy on this score, since he caused a wooden model of the right size to be made and placed upon the wall, in order to judge of its effect.
Taken as a whole, the Palazzo Farnese remains the most splendid of the noble Roman houses, surpassing all the rest in pomp and pride, though falling short of Peruzzi's Palazzo Massimo in beauty.
The catastrophe of 1527, when Rome was taken by assault on the side of the Borgo without effective resistance being possible, rendered the fortification of the city absolutely necessary.

Paul III determined to secure a position of such vital importance to the Vatican by bastions.
Accordingly he convened a diet of notables, including his architect-in-chief, Antonio da Sangallo.

He also wished to profit by Michelangelo's experience, remembering the stout resistance offered to the Prince of Orange by his outworks at S.Miniato.Vasari tells an anecdote regarding this meeting which illustrates the mutual bad feeling of the two illustrious artists.