Concini's diplomatic skills and political acumen (he prevented Appiani from allying France) brought him to the attention of Cosimo I de' Medici, who employed him as a trusted secretary and envoy around 1545.

[1] Concini effectively countered these accusations, asserting that Cosimo's actions were always guided by good intentions, aiming to support the emperor's prestige and maintain his influence in Italy.

Following the 1552 conspiracy orchestrated by Nicola III Orsini, Count of Pitigliano, and funded by France, which led to the removal of the Spanish garrison from Siena, Concini was once again sent to Charles V, this time accompanied by Pier Filippo Pandolfini.

Concini took credit for persuading the emperor that Cosimo was not involved in the events in Siena, instead placing the blame entirely on Diego Hurtado de Mendoza, 4th Count of Saldaña, the Spanish commander in July 1552.

Moreover, Concini maintained close contact with Gian Giacomo Medici during the war, participating in negotiations for the surrender of towns like Lucignano and Monteriggioni, and ensuring the duke was kept abreast of all developments.

Dispatched to Naples in 1556 to discuss the re-entry of Florentine exiles and war-related issues between the Papal States and the Duke of Alba, Concini was apprehended on his journey back under orders from Pope Paul IV (a member of Carafa family).

Concini's diplomatic skills also led to successful negotiations for cardinal hats for Cosimo's sons Giovanni (in 1560) and Ferdinando (in 1563), as well as for Angelo Nicolini (in 1565).

Famously, Concini redacted the 1561–1564 edition of Storia d'Italia (History of Italy) by Francesco Guicciardini and deleted a passage on the origins of the temporal power of the popes.

In 1565, Concini was again sent to the imperial court in Vienna, this time accompanying the duke's son, Francesco, to participate in the negotiations for his marriage to Joanna of Austria.

[1] After growing his influence, Concini's ancestors started to be associated with the ancient Ghibelline family of the Counts of Penna, who were exiled from Florence in 1303 and settled in Terranuova.