PC Joe Penhale, suffering from kidney stones, and Janice Bone, nanny to baby James Ellingham, are set to be married. This is the first wedding that Curate Rosie Edwards (Lucy Briggs-Owen) has ever officiated, but Joe is disappointed and nervous that a vicar is not officiating. Al Large is Best Man, but Penhale really wanted Martin to be Best Man. Bert hopes his whiskey enterprise will profit from pre-ceremony festivities. Aunt Ruth demands he provide her with documentation of expenses and sales on their whiskey enterprise, and finds the business is losing money. Wedding guests start fainting after they all drink directly from a bottle of Bert's whiskey they pass around. Martin diagnoses Joe with kidney stones and prescribes medication, but Joe refuses to take, fearing it might hinder the wedding ceremony. During the ceremony, Curate Edwards faints from nervousness. Janice has a change of heart about marrying Joe, and walks out on their wedding, leaving Joe with a broken heart.*After successfully rekindling their relationship, Louisa and Martin are living together again, but Louisa finds herself juggling too many responsibilities. Buddy the dog, who has been following Martin around for years, is finally allowed to stay because baby James Henry loves the dog.

After Janice jilts Joe Penhale at the altar, Martin and Louisa need to find a day care for James. After successfully counselling young student Astrid Trappett, Louisa considers becoming a child counsellor. Ken Hollister, landlord of the only pub in town, collapses, and Martin diagnoses him with leptospirosis bacterial infection, caused by the rats infesting his pub basement. Clive Tishell tests the pharmacy's new blood-pressure monitor on Al Large, which reveals Al's excessively high blood pressure. Ruth considers selling her farm. Receipts for the B&B's whiskey enterprise with Bert Large are not going as expected. John Rahmanzai, temporarily in town to scatter his late father's ashes, has an asthmatic attack and is saved by Martin, and also discovers that Ruth had an affair with his father long, long ago.[56]

Louisa's stress is compounded when she takes a group of students on a sailing trip. Ruth's decision about the farm causes trouble for the Large family enterprises, and so Morwenna and Al throw an event to help save the business. Clive drops dead but Sally is emotionless.

Morwenna's missionary parents pay her a surprise visit and are taken aback by her relationship with Al. Someone breaks into the school and vandalizes it. Buddy has a new friend, driving the Doc extra crazy. Bert is desperately lonely. Concerned at Morwenna's mum's appearance, Martin finds out from her that she's been diagnosed with terminal liver cancer, but is concerned that it may be a misdiagnosis. Dan Willis is back from Uni, acting strangely and suffering from shingles. Mary Rawlings pays a visit to the doc where nothing seems to be wrong. Louisa begins her psychology tutorials.[57]

With James teething, Martin and Louisa are desperate for more sleep, and take the advice of Mel Hendy (Rosie Ede) to let James chew on amber beads, but Buddy the dog ends up chewing on the beads, and James gets a bead stuck up his nose. Angela Sim's nephew Toby enrolls in Louisa's school. After Toby appears ill, Martin diagnoses him with scarlet fever. Al gets a new customer for the whiskey business but needs Bert's help, because he has no knowledge of how to operate the distillery equipment. Bert overhears Sally Tishell talking to herself in the back room. He advises her to acknowledge Clive's death, and get on with her life, but she shoos Bert away. Ruth also overhears Sally talking to herself, and asks Martin to pay her a visit. Bert is under increasing pressure from his employer/landlady to take their relationship from strictly professional to something much more intimate. Martin tells artist Walter O'Donnell he's in danger of losing his sight if he doesn't follow the doctor's orders. PC Penhale shuts down veterinarian Angela Sim's unlicensed goods and services business she's been operating out of the back of her car.[58]

James has started biting not only Louisa but other children at the nursery. Louisa is worried but Martin puts it down to his age. Student Tina Collins (Samantha Spiro) is a classmate of Louisa's, who has spoken to their lecturer about it too. Martin is not impressed and Louisa takes it personally when Martin says there is something wrong with Tina. But Martin is proved correct, when Tina collapses from taking Modafinil, a smart drug, used for treating sleep disorders. Louisa is in the car with Tina driving, Tina loses control and crashes the car. Martin says she almost killed his wife, and she's a menace to the public.*Penhale decides to have a police open house to raise community awareness, but local farmer Hannah Butler (Yolanda Kettle) arrives to file a complaint about theft of her sheep. Penhale is feeling so alone, that he asks for a session with Ruth to air his problems.*Morwenna leaves the surgery for a weekend away with Al at Hannah's camping site. Al is nervous to leave Bert running the pub but agrees. Hannah has orf (a viral skin disease which can spread to humans by handling infected sheep and goats) so cannot serve Al and Morwenna any food. Al decides to take matters into his own hands, which doesn't end well when he accidentally burns down the yurt.*Now there's only Emily helping Doc Martin, but she quits. Left on his own, Martin injures himself, tripping over Buddy. With Martin in an inflatable cast, Mrs Tishell insists she help out as receptionist. Local butcher Trevor Dodds (Richard McCabe) arrives for his annual physical. He also has developed Orf, which is highly contagious. Martin enlists the assistance of Penhale to find out the identification of every customer Dodds sold meat to, and to destroy the meat. When Penhale arrives, Dodds has tried to kill himself with a knife, necessitating Martin rush to the rescue. Mrs. Tishell fills in as Martin's surgery assistant while he patches up Dodds. Morwenna and Al hitch a ride back to town with Penhale.

Al and Morwenna participate in the annual gig race against another town. Louisa buys a new car, and Martin's blood phobia causes a disaster with a patient.

Martin stops practising the week before his hearing, but patients continue to solicit his advice. American tourist Beth Traywick (Sigourney Weaver) returns to the village and asks Mrs. Tishell for help, and Penhale commissions a bust of himself.