Many antihypertensive drugs have important interactions with drugs used for different purposes; when these are used concomitantly, adverse effects on blood pressure can result. Fortunately, in recent years, the drug development process has generally discouraged the approval and marketing of antihypertensive drugs with this problem, although some anomalies still exist (eg, telmisartan + digoxin). Physicians who work in emergency departments are more familiar with illicit or unregulated drugs that affect blood pressure; chief among these are cocaine and other opioids, and methylphenidate and its congeners. The most important prescription drugs that affect blood pressure are the nonsteroidal anti-inflammatory drugs (including selective inhibitors of the second isoform of cyclooxygenase) and steroids. Phenylpropanolamines, some antidepressants, and sibutramine can often be avoided, as they raise blood pressure in a significant proportion of those who take them. Conversely, the hypertensive effects of calcineurin inhibitors and erythropoietin are most commonly overcome by increasing the intensity of antihypertensive drug treatment, since these drugs are essentially unavoidable in most patients who receive them.