The Biondi Santi vineyard has 32 hectares (79 acres) of Sangiovese, of which five hectares (12 acres) were planted between 1930-1972. The vineyards are divided on five vineyard plots, located around the town of Montalcino.

The main estate, Tenuta Greppo, where the cellar and the main vineyards are located, lies at an altitude of 564 meters (1,850 feet) above sea level

The oldest vines form the basis of the Riserva wines, while the standard wine is made from vines in the 10-25 year bracket. Fruit from vines less than 10 years old supplies the dry, brightly aromatic Rosso di Montalcino.

The grapes are picked relatively early for the region, and then undergo a long maceration. Most of the grapes are fermented in resin-lined cement using native yeasts. Those destined for the Riserva are vinified in wooden vats.

The Brunello wines are then aged for 36 months in large, neutral Slavonian oak casks, while the Rosso wines see 12 months. Biondi Santi does not use new oak, as it is thought to add aggressive tannins to the naturally tannin-rich Sangiovese.

The wines tend to be fragrant and floral with savory hints, with bright berry and cherry fruit and peppery spice flavors over a backbone of fine tannins and acidity. Riservas are only released in the best years, can last for many decades, and often need 15 or more years to be tasted at their best.

The history of the estate and the entire region are closely related. Indeed, the first recorded mention of a Brunello was at Montepulciano's agricultural fair in 1869, referencing Clemente Santi's "vino rosso scelto (brunello) del 1865" (although the family's Greppo vineyards were well established by then).

The first wine to be officially labelled as "Brunello di Montalcino" was made in 1888 by Ferruccio Biondi Santi, Clemente's nephew. In 1932, the Italian Ministry of Agriculture referred to Brunello as "a recent creation of Dr Ferrucio Biondi Santi from Montalcino".

During the problems with oidium and phylloxera in late 19th Century, Dr Santi developed massal selections of his most resistant vines, later grafting them onto American rootstocks. He continued to make an oak-aged red from 100 percent Sangiovese while other producers disappeared or moved to different wine styles.

By the end of World War II, Biondi Santi's Tenuta Greppo was one of the few estates left in Montalcino, growing a specific variant of Sangiovese not seen in the rest of Tuscany. Much of the expansion of the appellation from 1970 is based on cuttings from their vines. The Biondi Santi clone BBS11, which was registered by Franco Biondi Santi in 1977, is commercially available today.

After Franco's death in 2013, the estate passed to his son Jacopo Biondi Santi. In 2016 he sold the estate to the French luxury holding EPI, owned by Christopher Descours, who is also the proprietor of Champagne Maisons Piper-Heidsieck and Charles Heidsieck, in addition to Château La Verrerie in Luberon.