The show revolves around Sam Stewart, the leader of a team of doctors serving the remote Hope Island Clinic. They look after residents of a small island community and neighbouring islands on the Great Barrier Reef, as well as holidaymakers and thrillseekers who visit the area. Sam is a single mother with an unusual interest in venom, hoping to extract the hidden secrets that may have the power to cure fatal diseases.
Dr Sam Stewart runs a remote medical clinic on Hope Island in the Great Barrier Reef. She's a GP, but in her spare time she and her colleague, Gus, chase the venomous creatures that inhabit the area. A new doctor arrives on the Hope Island to assist Dr. Sam Stewart at her medical clinic, although his introduction becomes a bit of a revelation to him. A scuba diver comes up too quickly and suffers from the bends.
Sam and Gus go on a monitor lizard hunt while the new doctor, Rick, has trouble adjusting to working in a remote clinic. Meanwhile, a new bride on her honeymoon steps on a deadly stonefish.
Sam goes to the mainland to give a lecture to medical students on tropical medicine where Andrew tries to get her to transfer to the mainland, again. A young girl is brought into the clinic going into anaphylactic shock after being bitten.
It's Freya's day off so Sam and Gus take her on a hunt for some venomous spiders when Gus falls into a Gympie stinger bush. Then Freya and Sonny are snorkelling when he has a diabetic attack and becomes unconscious.
It's a busy monthly clinic day on Hope Island and Rick is keen to see some new patients. Sam and Livvy try to get him to improve his bedside manner and listen to their complaints. A know-it-all amateur herpetologist causes chaos when a snake is let loose in the clinic.
Sam has a meeting with her Andrew over an upgrade to Hope Clinic but is not happy when she finds out the money is coming from a research foundation. A woman starts chasing Rick after a night at a karaoke bar.
Toby goes diving alone and runs into some trouble with sharks. Sam is determined to find out why. Rick and Freya are hitting it off but she is much more active and adventurous than he is. Gus and Olivia are also getting on well together.
Sam is happy when she receives the news that the Foundation is to fund a trial of her venom ulcer cream. However, this turns to dismay when she finds out that Malcolm is to run the trial. He comes to the island to inspect the facilities.
Two old friends of Sam and Jack, renowned husband and wife wildlife film-makers, have come to Hope Island. While filming their latest TV series tragedy strikes them. A massive search and rescue operation on the reef is mounted.
Sam has arranged a ceremony to scatter her beloved Father's ashes. Much to Jack's dismay, Andrew is bringing his girlfriend and her daughter and he predicts the event will end in disaster.
A wild storm heralds the coming wet season and damages the clinic's satellite dish. Meanwhile, Freya is initially intrigued to learn something of Rick's past.
Toby discovers a relic from a shipwreck that should triple in value all the artifacts he has collected so far. An excited Erica flies out to see the piece.