In 1565, on the resignation of Cipriano de Rore, Zarlino took over the post of maestro di cappella of St. Mark's, one of the most prestigious musical positions in Italy, and held it until his death.
While he was a moderately prolific composer, and his motets are polished and display a mastery of canonic counterpoint, his principal claim to fame was his work as a theorist.
His exposition of just intonation based on proportions within the "Senario" (1, 2, 3, 4, 5, 6) and 8 is a departure from the previously established Pythagorean diatonic system as passed on by Boethius.
He was also one of the first theorists to offer an explanation for the prohibition of parallel fifths and octaves in counterpoint, and to study the effect and harmonic implications of the false relation.
Translations and annotated versions were common in France, Germany, as well as in the Netherlands among students of Sweelinck, thus influencing the next generation of musicians who represented the early Baroque style.