Danza and Milano will reprise their roles as Tony and Samantha Micelli, respectively.
The sequel will take place 30 years after the original and follow Samantha, who is a single-mom living in the same house from the first series. The program will also follow Tony, who is now retired, and his relationship with his daughter.
Who's the Boss?, created by Martin Cohan and Blake Hunter, ran for eight seasons on ABC from 1984 to 1992. Norman Lear is executive producing the sequel along with Danza and Milano.
"Who's the Boss? was a very progressive show. A divorced mom, who owned her own business and had a free-spirited mother who made sex jokes, who hires a single dad to be her housekeeper. We were really a modern family in the 80s. We look forward to making the sequel as thoughtful, smart and relevant to the times today. And make people laugh at the same time," Milano said in a statement to Entertainment Tonight.
"We feel the time is right to tell the story of where these amazing characters are today. Can't wait to share their stories with you. So happy," Milano said on Instagram alongside a photo of herself with Danza from the show.
Danza also commented on the revival on Instagram alongside a number of photos from the show.
"Very excited to bring Who's the Boss back to television!" the actor said.