He used his keynote speech at the Lib Dems conference in Aviemore today to declare that Ms Robison must "carry the can" for a string of problems in the health service. This includes the recent NHS Tayside row over charity cash being used to fund IT systems, instead of frontline care as intended.
Labour leader Richard Leonard also demanded Ms Robison's departure at Holyrood yesterday, but Nicola Sturgeon is backing her long-term friend and political ally.
“A clear symptom of a stale government," he said
“A chairman and chief executive used as human shields for the health secretary.
“How can it be right for the people brought in after the mistakes to carry the can alone for those mistakes?"
Mr Rennie added: "Because of NHS Tayside, because of the shortage of GPs, the failures in social care, failures in A&E, failures in waiting times, failures in mental health, I am fed up with it.
“These failures must mean change must come. We should not expect things to just carry on.
“I don’t often call for resignations. Shona Robison must accept that she is responsible. Change will only come when there is change at the top.
“She must resign. And she must resign now.”