Implementing personalized cancer care requires a sound understanding of cancer genomics, familiarity with the analytical methods used to study cancer, knowledge of the mechanisms of action of targeted drugs, and ways to assimilate and understand complex data sets. Perhaps the greatest challenge is obtaining the drugs predicted to be beneficial based on the genomic profile of a patient's tumour. A potential solution is creation of a national facilitated access programme and registry for off-label use of targeted anti-cancer drugs. Within such a programme, patients could receive the targeted agent matched to the genomic profile of their tumour. Physicians would receive guidance in interpretation of complex genomic tests and access to drugs. Pharmaceutical companies, payers and regulators would receive data on off-label drug and test use and clinical outcomes to inform their research and development plans and coverage decisions and to track real-world safety. Although recently launched prospective clinical trials will determine the true benefit of matching drugs to genomic alterations, the approach proposed here will facilitate delivery of personalized medicine services to participating patients while at the same time making observations that allow us to learn from each patient to inform clinical care and future research initiatives.