Although the medical and technological revolution in the last three decades has improved clinical outcome in patients presenting with acute STEMI, residual morbidity and mortality are still high. The critical role of treatment delay and optimal sustained patency are prerequisites of successful reperfusion. Clinical efficacy of successful reperfusion has been repeatedly demonstrated. Nevertheless, the ideal pharmacological and mechanical reperfusion methods are still a matter of major debate. Dependent on the local situation, either immediate thrombolytic therapy or fast transfer to an experienced high-volume tertiary care centre for PPCI has to be preferred. According to the mortality data, pre-hospital but also in-hospital thrombolysis has success rates comparable with PPCI when intitiated within the first 2-3 h after the onset of pain. Therefore, in these patients, thrombolytic therapy should not be withheld in favour of mechanical reperfusion if it cannot be offered within 90 min. The situation seems to be somewhat different in patients presenting later than 3 h after the onset of pain. These patients have a mortality rate of ∼6-8% when treated by mechanical reperfusion. Mortality rates increase exponentially with every hour delay, when treated with thrombolysis. In contrast, for patients with a longer delay from symptom onset, a further time delay for transfer to a tertiary care hospital with catheter facilities seems to be acceptable and less deleterious. Outcomes can be further improved by pre-hospital administration of lytic therapy when transportation and organization delays for PPCI can be expected. Whether or not immediate PCI should be performed following hospital arrival in patients with clinical signs of successful lysis is still not fully clarified. Although the advantages of pre-hospital thrombolysis have been well-known for many years, this therapy has not become a common practice for various reasons. This is a missed opportunity for many patients, especially those in rural areas, requiring long transportation times to the referral hospitals, although thrombolysis, when left alone, is still a suboptimal therapy. Efforts should therefore be made to improve this situation, wherever possible, by organizing quick transportation to centres equipped for PPCI and with an experienced staff. Investigations have clearly shown that a well-organized pre-hospital pharmacological reperfusion strategy can save lives and positively influence other clinical outcomes. Besides pre-hospital thrombolysis, and because of better overall results, especially pre-hospital 'facilitation' of PCI is currently under investigation. Facilitation can be performed theoretically by use of thrombolytic drugs, by use of a combined approach (thrombolytics 1/2 dose + GP IIb/IIIa-inhibition; now fallen mostly out of credit), or by pre-treatment with GP IIb/IIIa-blockers alone. The combined use of pharmacological and mechanical reperfusion might be the optimal treatment principle, but still questions with regard to safety (major bleeding complications), particulary in older patients, and of efficacy remain unsolved. Alterations in the dosages of the various antithrombotic agents have to be further tested before pre-PCI pharmacological treatment can become a general treatment option. © The European Society of Cardiology 2005. All rights reserved.