Rebellion in Ireland signaled a need for the New Model Army to march again.
Cromwell was appointed as commander.
Cromwell appears to have approached this campaign in a different way to his others. Like many Englishmen of the time he was deeply suspicious of Catholic Ireland, he regarded the Irish as dangerous enemies because of the political strength of the Pope rather than religious concerns (it was the Pope who had enouraged King Phillip of Spain to attempt invasion), but even then he usually erred on the side of humanity.
However at Drogheda the defending garrison refused to surrender and was put to the sword. Disdain for the Irish still does not fully explain this as the garrison commander Sir Arthur Aston and much of the garrison were in fact English, neither were they all Catholic, many Royalists in Ireland were Protestant.
There was at the time an article of war that stated that when a defending garrison had had a breach blown in it's defences, it was in order for the attacking force to give no quarter.
This is because to storm a breach in a wall requires almost superhuman/suicidal bravery. Troops which succeed will have necessarily sustained heavy losses and are therefore much more inclined to blood lust. Wellington was arguing the same point as late as 1814 following the storming of various forts such as Cuidad Rodrigo and Badajoz. Another famous example would be the Alamo in the war between Texas and Mexico.
The next town attacked was Wexford. Depressingly the same thing occurred there. Slaughter of the Garrison which Cromwell does not seem to have tried to prevent.
Although many claim that innocent civilians were slaughtered during the storming of both towns, there seems little historical evidence for this. Especially as prior to Drogheda Cromwell had decreed that the populace were not to be harmed. He even had two of his own men hanged for stealing from locals.
It is also worth noting that similar atrocities had been occurring on the mainland of Europe during the 30 years war.
Whatever the truth, Catholics and the Irish have never forgotten the slaughters of Drogheda and Wexford. There is no doubt that Cromwell conducted this campaign in an efficient but completely ruthless way.