The firm's attorneys focus on health care, finance, real estate, technology, private equity and life sciences.

In 2000, Polsinelli created a Science and Technology group with patent and business attorneys focused on the emerging biotech industry.

On February 1, 2009, the 300-attorney Polsinelli firm merged with Shughart Thomson & Kilroy, P.C., a 180-lawyer Kansas City-based, regional law firm with a national trial reputation and a business practice July 1, 2011, Polsinelli expanded into California via its acquisition of the attorneys and staff of Quateman LLP, California's largest women-owned bond counsel firm founded in 1989 by Lisa Greer Quateman.

In March 2016, Polsinelli welcomed 44 intellectual property attorneys led by Gregory Novak and Tracy Druce, including Q. Todd Dickinson, from the national boutique firm Novak Druce Connolly Bove + Quigg., forming one of the largest IP practices in the nation and opening offices in Houston, Boston and Silicon Valley.

[5] In 2012, it announced plans to tear down the bankrupt and unfinished Moshe Safdie-designed West Edge building that had originally been built for Bob Bernstein on the west side of the Plaza and replace it with a 10-story structure designed by 360 Architecture called Plaza Vista.