Nonpharmacogenetic factors may play a key role in the success of oral endocrine therapy for breast cancer. Adherence, defined as following medical advice as well as persistence and duration of use for patients prescribed endocrine therapy, may impact significantly on recurrence and survival. Side effects from tamoxifen or aromatase inhibitors may lead to patients stopping or switching therapy, while comorbidities, consequent coprescribing and patient perceptions may also influence outcomes. Interventions to improve adherence and persistence are required and could have as great an effect on survival as applying pharmacogenetic principles to the endocrine management of breast cancer.