He has previously played in Major League Baseball (MLB) for the Florida/Miami Marlins, San Diego Padres, Cleveland Indians, Washington Nationals, Toronto Blue Jays, New York Mets, Philadelphia Phillies, Colorado Rockies, and Atlanta Braves.

After struggling with arm fatigue and pitch delivery issues in 2019, Hand was perfect in 16 save opportunities for Cleveland in 2020, but he was designated for assignment at the end of the year.

[5] He was promoted to the Class A-Advanced Jupiter Hammerheads to begin the 2010 season,[13] and by mid-June, he led the team with a 4–3 record, 3.33 ERA, and 74 strikeouts in 75+2⁄3 innings.

[16] The Marlins, who were in need of an additional starting pitcher when Josh Johnson was placed on the disabled list, promoted Hand to Florida on June 6, 2011.

[19] He received three more major league promotions between July and September, but was sent back down both times as he struggled both with controlling his pitches and with allowing home runs.

With the team out of playoff contention by September, however, manager Jack McKeon sent Hensley back to the bullpen and allowed Hand to start the final stretch of games and sell himself as a major league player for the 2012 season.

[27] The MLB collective bargaining agreement allowed a player like Hand to join a team as the 26th person on their 25-man roster for a same-day doubleheader as long as he was sent back to the minors the next day.

[31] After the Marlins used 11 pitchers in a 15-inning game against the New York Mets on April 30, Hand was briefly promoted to Miami as a fresh arm,[32][33] but he was sent back down two days later after making one relief appearance.

[36] He spent nine weeks on the disabled list; on July 30, his first start since returning from the injury, Hand held the Colorado Springs Sky Sox to three hits in five scoreless innings, earning a no decision.

[23] After spending spring training in contention with Tom Koehler and Brian Flynn for the final spot in the Marlins' starting rotation,[42] Hand, who went 2–1 with a 2.70 ERA in exhibition games, made Miami's Opening Day roster as a reliever.

[45] When he returned from his rehabilitation assignment in July, Hand was added to the starting rotation, which had lost both the injured José Fernández and struggling Jacob Turner, the latter of whom had become the team's new long reliever.

[23] In 2015, Hand and the newly acquired David Phelps spent spring training preparing as backup starters in case the Marlins quickly lost a member of their rotation to injury, as they had the season prior.

Hand earned a no decision as he held the Pirates to four hits in five innings, but the Marlins lost 5–2 after poor outings from relievers Mike Dunn and Sam Dyson.

[50] After allowing six runs to the Toronto Blue Jays in an 11–3 loss on June 8, Hand did not start a game again until August 5, when he pitched four scoreless innings and left the Marlins with a 1–0 lead against the Mets.

Hand was the first Marlin in franchise history to record two RBI sacrifice bunts in one game and was the first MLB player to do so since Alex Cora 11 years prior.

[65] Primarily a setup man, Hand received his first save opportunity of the season on May 24, when he exchanged places with struggling closer Brandon Maurer.

Hand came into the game in the ninth inning with the bases loaded and escaped the outing with two strikeouts and a flyout, helping the Padres defeat the Mets 6–5.

[69] He was officially named as the team's 2018 closer during spring training, but he also made appearances in other high-leverage situations, such as when the Padres faced the heart of the Colorado Rockies' lineup – Charlie Blackmon, Nolan Arenado, and David Dahl – in the seventh inning of a game.

[23] On July 19, 2018, the Padres traded Hand and Adam Cimber to the Cleveland Indians, who were poised to lose several relievers to free agency during the 2018–19 offseason, in exchange for catching prospect Francisco Mejia.

[75] On his new team, Hand became a setup man for Cleveland closer Cody Allen, who had 19 saves on the season but had blown several attempts, including a game that Trevor Bauer left 4–0 against the Cincinnati Reds that ended in a 7–4 loss for the Indians.

[76] By late August, while Allen remained the de facto closer for the Indians, Hand, who allowed only two earned runs in 14 appearances, was receiving save opportunities.

[82] He was 22-for-22 in save opportunities until June 25, when Hunter Dozier hit a grand slam against Hand in the ninth inning of the Indians' game against the Royals, giving Kansas City a three-run lead.

[86] Following a stretch of 19 games in which Hand allowed 12 earned runs on 26 hits for a 6.00 ERA, the Indians sent their pitcher back to Cleveland in the middle of a road trip to undergo medical imaging.

[92] At the end of the season, Hand was named to the All-MLB Second Team and was a finalist for AL Reliever of the Year,[93][94] an award which ultimately went to Liam Hendriks of the Oakland Athletics.

He first allowed Gary Sánchez to tie the game on a sacrifice fly that brought home Mike Tauchman, and then DJ LeMahieu hit an RBI single to score Gio Urshela from second base, giving the Yankees a 10–9 lead.

[101] The Washington Nationals, who had lost their only left-handed reliever after Sean Doolittle became a free agent that offseason, signed Hand to a one-year, $10.5 million contract on January 26, 2021.

[109] He could not find success with his new team: his first 11 appearances for the Blue Jays included two losses, a blown save, and a walk-off walk to the Seattle Mariners.

Because he was not with the team on September 1, Hand was ineligible to appear in the postseason for the Mets, but was added to the bullpen to help them clinch a potential playoff berth in the final month of the regular season.

[114] Hand made 16 appearances for New York in September, and while he had a 1–0 record and 2.70 ERA, he also allowed five of the six runners he inherited to score, and the Mets stopped placing him in high-leverage situations as a result.

[118] He saw increased usage in August when Corey Knebel and Seranthony Domínguez were both sideliend with injuries,[119] before landing on the injured list with left elbow tendinitis at the end of September.