The use of herbs or botanicals is markedly increasing worldwide. Herbs are frequently administered in combination with medications, potentially increasing herb-drug interactions and overall effects. These effects can occur due to incorrect use, lack of knowledge, and awareness regarding the active ingredients involved. As herbal products are perceived as safe, patients usually self-administer herb products without informing their doctors, pharmacists, or healthcare providers. This is particularly true for elderly patients, who typically take a lot of medications alongside herbal products with a combination of poorly defined ingredients. Herb-drug combinations can elicit adverse effects when herb compounds regulate drug-metabolizing enzymes, transporters, and others. A systematic approach and regulatory measures are necessary against unwanted consequences. This chapter explores herbs, active compounds, and drugs with mechanistic targets that are relevant to interactions.