A variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents either cause sodium retention and extracellular volume expansion or directly or indirectly activate the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, and an increase in pressure may be encountered after their discontinuation. In general, these pressure increases are small and transient; however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and direct to the optimal antihypertensive therapy. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action.