Nicola Sturgeon is stepping down as Scottish Health Secretary at Holyrood to play a major role in the run-up to the independence referendum.
She will become Infrastructure, Investment and Cities Secretary, focusing on economic recovery.
Ms Sturgeon, who remains Scotland's Deputy First Minister, will also take lead responsibility for government strategy and the constitution, which includes preparations for the independence referendum planned for 2014.
Ms Sturgeon has had the health brief since the SNP came to power in 2007 - making her the longest-serving Scottish health secretary.
Alex Neil, the current Infrastructure and Investment Secretary, will take over her old position.
Bruce Crawford, who played a key role in talks over the staging of the independence referendum in his position as Parliamentary Business and Government Strategy Secretary, is to retire from the Government.
The reshuffle is the first time First Minister Alex Salmond has changed his Cabinet team since the SNP's landslide victory at the 2011 Holyrood elections.
As the changes were announced, Mr Salmond said: "As Health Secretary, Nicola Sturgeon has demonstrated what can be achieved when Scotland has responsibility for its own affairs. She has delivered record-low waiting times and protected the NHS from the creeping privatisation of the UK Government. As Cabinet Secretary for Infrastructure, Investment and Cities, she will have a lead role in our programme for economic recovery. With responsibility for government strategy and the constitution, she will also lead in making the positive case for Scotland's future."
Mr Neil "delivered the biggest infrastructure investment programme in Scotland's history against a backdrop of budget cuts from Westminster", the First Minister said. "In taking forward Nicola Sturgeon's substantial achievements as Health Secretary, he will ensure that Scotland's health service continues to have the strongest possible leadership," Mr Salmond said.
In her new job, Ms Sturgeon is expected to meet Scotland Office minister David Mundell on Thursday for talks about how the referendum should be staged.