In 1999, Busuttil was appointed Head of the Malta-EU Information Centre (MIC) and led Malta's public awareness campaign ahead of the 2003 EU membership referendum.

[16] But his strongest contribution was within the Civil Liberties, Justice and Home Affairs Committee where he was the Coordinator (Spokesperson) for the EPP Group and covered issues that include the sensitive areas of common European immigration and asylum policy.

[24] Busuttil's term as Leader of the PN and of the Opposition was characterised by a his choice to champion the rule of law and the fight against corruption in Malta.

In April 2017, he published a leaked report that implicated the Chief of Staff in money laundering activities linked to Malta's golden passport scheme.

The following month, in May 2017, Busuttil published yet another leaked report and presented evidence of alleged illegal transfers to the tune of €650,000 paid by Keith Schembri to the former Managing Director of The Times of Malta, Adrian Hillman.

[25] The revelations increased pressure on the Labour Government and Prime Minister Joseph Muscat and eventually led to an early election being called on 1 May 2017.

In February 2018, Delia appointed Busuttil as Shadow Minister for Good Governance, asking him to continue his fight for the rule of law.

[36][37] Nevertheless relations between them turned sour when Delia asked Busuttil to resign from the PN parliamentary group in the wake of the news of the publication of the conclusions of the 'Egrant' magisterial inquiry into the alleged ownership of one of the Panama company by the Prime Minister's wife, which concluded that no proof was found that Egrant belonged to the Prime Minister's wife although the inquiry did not find details of the actual owner.

[40] Other MPs that lent their name to this cause included Claudette Buttigieg, Therese Comodini Cachia, Marthese Portelli, Claudio Grech, Karol Aquilina, Karl Gouder and Jason Azzopardi, as well as MEP David Casa.

Replies to a series of parliamentary questions revealed that a total of €49,015.56 were awarded by the Ministry for Transport and Infrastructure and its entities to Europa Research and Consultancy Services Ltd, of which Opposition leader Simon Busuttil was the founding director.

[45] Additionally, Busuttil benefitted from more than €1,500,000 [clarification needed] which was also confirmed by the Court of Justice, losing a libel case against Partit Laburista.[when?