The collision involved a Silver Audi and a red Ford at around 11.20pm yesterday on an unclassified road between St Madoes and Errol in Perthshire.
The 44-year-old man driving the Ford died at the scene of the crash, while two men, aged 35 and 31, who were travelling in the Audi were seriously injured and taken to Ninewells Hospital in Dundee for treatment.
Police are continuing to investigate the circumstances of the crash and asked any witnesses to contact them on the non-emergency 101 number.
As with all deaths, a report will be submitted to the procurator fiscal.
Meanwhile, police in Edinburgh are appealing for witnesses after a motorbike crashed into a bus stop yesterday injuring three people.
The motorcyclist and his passenger were seriously injured and a pedestrian waiting at the bus stop in Dalry Road was also slightly hurt in the accident.
All three people were taken to Edinburgh Royal Infirmary for treatment, with both people travelling on the bike said to be in a serious condition.
Sergeant Alan Stewart said: "Dalry Road was quite busy at the time of the incident, and I would appeal for anyone who saw what happened, or the motorcycle just before it crashed, to contact Police Scotland on 101 or through Crimestoppers on 0800 555 111."