The accepted message is that humankind has largely conquered infectious disease with a mixture of antibiotics and vaccines, yet it is becoming increasingly clear that chronic hidden or latent infections (crypto-infections) lie behind many of today’s big killers, including heart disease, dementia, and cancer. As an exemplar of how the organisms responsible can hide in plain sight, causing devastation while the medical world is in denial, —the bacterium responsible for Lyme disease—has led Dr Perronne to clash with his fellow specialists in infectious disease (ID) and challenge the status quo. From his experience as one of France’s, and the world’s, leading ID specialists, he examines the threats that both Lyme in particular and crypto-infections in general pose and how we can rise to the challenge.