Best Medicine Season 2 Episode 1 Preview: Air Date, Cast, Photos & Trailer

Fox’s popular dramedy Best Medicine returns for season two on Tuesday, September 22, 2026 at 8pm ET/PT. The series immediately caught on after its January 2026 premiere and received an early renewal in March.

Josh Charles returns to star as Dr. Martin Best, Abigail Spencer is back as Louisa Gavin, Josh Segarra reprises his role as Sheriff Mark Mylow, Annie Potts stars as Aunt Sarah, and Cree returns as Elaine Denton. Also returning for season two are Stephen Spinella as Greg Garrison and Jason Veasey as George Brady, upped to regulars for the new season.

Season 2, Episode 1, “Be Careful What You Fish For” Plot: While Martin continues to struggle with his blood phobia, a mermaid washes ashore in Port Wenn to the amazement of everyone in town. Meanwhile, Judith, a well-meaning townsperson (guest star Andrea Martin), creates havoc while on prescribed oxygen, Louisa continues to see Martin’s girlfriend, Eden, for medical guidance, and Greg and George’s success from the seas urchin boom takes its toll on the both of them.

Best Medicine Plot, Courtesy of Fox:

Martin Best is a brilliant surgeon who abruptly leaves his illustrious career in Boston to become the general practitioner in a quaint East Coast fishing village where he spent summers as a child. Unfortunately, Martin’s blunt and borderline rude bedside manner rubs the quirky, needy locals the wrong way, and he quickly alienates the town, even though he’s all they’ve got.

Although Martin can expertly address any medical ailment or mystery in this idiosyncratic town, he’s really just desperate to be left the hell alone. Instead, he keeps getting dragged right smack into the middle of their personal chaos, feuds, and fantasies. What the locals don’t know is that Martin’s terse demeanor masks a debilitating new phobia and deep-seated psychological issues that prevent him from experiencing true intimacy with anyone. But tenacity is the creed of everyone in their small village, and the people who live there may be exactly what the doctor ordered.