Lord Grenville was invited to form a ministry on the death of Pitt the Younger. He was reluctant to do so but eventually agreed to form a cross-party alliance of MPs which became known as the "Ministry of all The Talents". It was a coalition between Grenville's supporters, the Foxite Whigs, and the supporters of former Prime Minister Lord Sidmouth. Grenville, as First Lord of the Treasury, and Fox, as Foreign Secretary, were joint leaders.
The ministry was largely unsuccessful, failing to make peace with France or to accomplish Catholic emancipation. It did, though, result in one momentous achievement - the abolition of the slave trade in 1807.
The end of his term foundered on the perennial issue of Catholic emancipation. when he was forced to tender his resignation with obvious relief.