Cytochrome P450 2D6 (CYP2D6) accounts for only <4% of all hepatic CYPs but metabolizes 25% of current drugs such as antidepressants, antipsychotics, antiarrhythmics, antiemetics, beta-adrenoceptor antagonists and opioids. The CYP2D6 activity varies considerably within a population and includes ultra rapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The clinical consequence of the CYP2D6 polymorphism can be either occurrence of ADRs or altered drug response. About 25 million Ethiopians are UMs according to studies and therefore will have no drug response when a standard dose of drugs metabolized by CYP2D6 predominantly are used. These have been evident in a number of studies in which UMs were found non-responders at ordinary dosage. Genotyping for individuals receiving drugs that are metabolized by CYP2D6 may help clinicians avoid ADR and loss of therapeutic outcome by individualizing treatment. Screening for polymorphisms is cost-prohibitive in Ethiopia and is not yet recommended but it is currently most advanced in Scandinavian countries.