Drug therapy is essential when caring for elderly patients, but clearly it is a double-edged sword. Elderly patients are at high risk of having drug interactions, but the prevalence of these interactions is not well documented. Several types of interactions exist: drug-drug, drug-disease, drug-food, drug-alcohol, drug-herbal products, and drug-nutritional status. Factors such as age-related changes in pharmacokinetics and pharmacodynamics, frailty, interindividual variability, reduced homoeostatic mechanisms, and psychosocial issues need to be considered when drug interactions are assessed. Software can help clinicians to detect drug interactions, but many programmes have not been updated with the evolving knowledge of these interactions, and do not take into consideration important factors needed to optimise drug treatment in elderly patients. Any generated recommendations have to be tempered by a holistic, geriatric, multiprofessional approach that is team-based. This second paper in a series of two on prescribing in elderly people proposes an approach to categorise drug interactions, along with strategies to assist in their detection, management, and prevention.