As the determination of gene sequences and their function gains speed at the dawn of the third millennium, biomedical research efforts are oriented towards definition of the genetic and molecular expression patterns that may drive different disease. A major part of these efforts is addressed to the definition of inter-individual variations that are expected to become integral for treatment planning, in terms of efficacy and adverse effects of drugs. It is this thrust on genome-based 'rational therapeutics' that is hoped to progressively lead to the era of 'personalized medicine'. This approach uses the technological expertise from genomics and functional genomics to define, predict and monitor the nature of the response of an individual to drugs, and to rationally design newer drugs. In the present review we will conduct our readers through an understanding of the fundamentals of pharmacogenomics and of the technologies currently available that are advancing this relatively new science. Conversely, there are issues raised that concern how medical practice is preparing itself to implement new alternatives for therapeutical interventions and finally, how to respect patient confidentiality and rights.