It has become apparent that noncardiovascular drugs can affect blood pressure (BP) in an off-target manner, either by raising or lowering pressure or by negating the beneficial hypotensive effect of concomitantly prescribed antihypertensives. This paper presents compelling evidence that ambulatory blood pressure monitoring (ABPM) should be used to detect BP effects during the development of noncardiovascular drugs. The requirements for standardizing ABPM to obtain the most information from the least number of participants and the many advantages of obtaining a 24-hour BP profile are discussed. The use of ABPM in trials of antihypertensive agents, though differing in purpose (the demonstration of BP-lowering efficacy) from the use of ABPM in trials of noncardiovascular drugs (the demonstration of any off-target effect on BP) nonetheless provides methodological similarities that can be applied in both contexts with advantage. The paper also considers whether there are lessons to be learned from a regulatory science approach that is designed to prospectively identify unacceptable off-target cardiac effects of noncardiac drugs and offers some thoughts on how a future paradigm of standardized use of ABPM to assess off-target BP effects during the development of noncardiovascular drugs might benefit patient safety.