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Mosley is married to Clare Bailey, a GP; they have four children. He has reversed his Type 2 diabetes with diet. In a BBC documentary on sleep, Mosley revealed he has chronic insomnia. He published Fast Asleep in 2019.

He presented Blood and Guts, Medical Mavericks and The Story of Science for television, and was the subject of a television documentary, 10 Things You Need to Know about Losing Weight. He presented Make Me for BBC One. In April–June 2010 he produced and presented the television series The Story of Science: Power, Proof and Passion broadcast by BBC Two.

In January 2013, he presented The Genius of Invention. In the documentary named The Truth About Personality, first aired on 10 July 2013, Mosley explores what science can tell us about optimism and pessimism and whether we can change our outlook.

His documentary The Truth About Exercise, shown first in 2012, aired current thinking about how different patterns of exercise might help achieve health benefits, the danger of sitting for prolonged periods and revealed how certain genotypes are unable to gain significant improvements in aerobic fitness (VO2 max) by following endurance exercise programmes. His own genetic type can gain many of the benefits of exercise, primarily improved insulin response, through short, high-intensity training sessions as suggested by the research of Professor James Timmons.

Mosley is credited with popularising the 5:2 diet, after appearing in August 2012 in the BBC2 Horizon documentary Eat, Fast & Live Longer. In early 2013 he published The Fast Diet with Mimi Spencer.

In 2011 he made a series entitled The Brain: A Secret History, on the history of psychology and neuroscience. During the series, while studying the methods that are being employed to identify the brain structure of psychopaths, his personal tests revealed he himself shared these same brain traits. In the same year, he made a two-part documentary, Frontline Medicine with episodes called "Survival" and "Rebuilding Lives". These programmes focused on the medical advances in the treatment of military personnel during the 10 years of war in Iraq and Afghanistan and examine how these new techniques are being utilised in emergency medicine for civilian casualties in the United States and Great Britain.

He produced a number of science programmes, including The Human Face, three series with Professor Robert Winston, and the 2004 BBC Two engineering series Inventions That Changed the World hosted by Jeremy Clarkson.

He was nominated for an Emmy and BAFTA for his Horizon documentary reporting the link between Helicobacter pylori and gastric ulcers discovered by Australian scientists, Robin Warren and Barry Marshall. He was named Medical Journalist of the Year in 1995 by the British Medical Association.

Upon graduation, having become disillusioned by psychiatry, Mosley joined a trainee assistant producer scheme at the BBC in 1985.

Michael Mosley (born 22 March 1957) is a British television journalist, producer, presenter, and qualified doctor who has worked for the BBC since 1985. He is probably best known as a presenter of television programmes on biology and medicine and his regular appearances on The One Show.