Pressman has been described by The Guardian as a "high profile diplomat"[2] and by CNN "one of the world's leading human rights advocates".

[4] Pressman joined Clooney in founding Not On Our Watch Project, an advocacy and grant-making organization focused on raising awareness about mass atrocities.

[4] Under President Barack Obama, Pressman served as an assistant secretary in the Department of Homeland Security, where he was responsible for policy development on global criminal justice issues.

[21] Pressman led United States negotiations with China resulting in a package of multilateral sanctions in response to nuclear activities on the Korean Peninsula.

[25] As a spokesperson for the US, he praised the lifting of sanctions against Liberia as evidence of their success[26] and denounced the failure of Sudanese authorities to take advantage of the support provided by the international community.

[27] The day after a Orlando nightclub shooting in June 2016, Pressman told the UN General Assembly that denouncing terrorism was an insufficient response: "If we are united in our outrage by the killing of so many — and we are — let us be equally united around the basic premise of upholding the universal dignity of all persons regardless of who they love, not just around condemning the terrorists who kill them."

He was influential in winning UN Security Council approval of a resolution that condemned "targeting persons as a result of their sexual orientation."

"[31] His clients at Boies included Epic Games Inc., the New York Yankees Partnership, and Centene Corp.[32] In June 2020 he moved to Jenner & Block, again as a partner based in New York City,[33][34] where his clients included Princeton University, First Republic Bank, and the Oshkosh Corp. Pressman was on Jenner's team of attorneys suing Russian banks in U.S. federal court in case over Malaysia Airlines Flight 17 in 2014.

[38] In October 2018, Pressman protested the U.S. State Department's new policy under Pompeo that denied visas to the same-sex partners of foreign employees of international institutions like the United Nations and the World Bank unless they were married.

The State Department said the policy change was designed "to help ensure and promote equal treatment" between straight and gay couples"; Pressman called it "creative and cynical way to use the expansion of equality at home to vindictively target same-sex couples abroad," given that many of them were denied the right to marry in their home countries.

He was regularly attacked by prominent Fidesz politicians and the Fidesz-controlled state media, which produced a highly "unusual" diplomatic situation between two NATO allies.

[46] Pressman was particularly critical of the Fidesz government's close relationship with Beijing,[47] pervasive public corruption,[48] efforts to restrict LGBT rights in Hungary, of Orbán's perceived closeness to Russian leader Vladimir Putin,[49][50] and of Orbán's support for Donald Trump in the 2024 U.S. presidential election.

"[52] Some observers viewed Pressman's sexuality as particularly problematic for Fidesz given the party's messaging around defending traditional family values.